Advisory Group recommendations on priorities for the IARC Monographs during 2025–2029: Radiofrequency electromagnetic fields including wireless mobile radiation

Advisory Group recommendations on priorities for the IARC Monographs during 2025–2029
iarc.who.int, 4 November 2024

Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2025–2029 (pp. 171-173)

Radiofrequency electromagnetic fields including wireless mobile radiation

Current IARC/WHO classification

Radiofrequency electromagnetic field (RF-EMF) radiation (including from wireless mobile telephones) has been previously classified by IARC as possibly carcinogenic to humans (Group 2B) in IARC Monographs Volume 102 in 2011 (IARC, 2013a), based on limited evidence in humans for glioma and acoustic neuroma. RF-EMF was given a priority rating of high by the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 (IARC, 2019a), on the basis of new cancer bioassay evidence in two independent studies (described below).

WHO is undertaking a health risk assessment of RF-EMF for a variety of outcomes, including cancer. This will be published as a monograph in the Environmental Health Criteria series and is based on several, currently ongoing, systematic reviews commissioned by WHO (Lagorio et al., 2021; Mevissen et al., 2022).

Exposure characterization

In IARC Monographs Volume 102, RF-EMF radiation was defined as radiation in the frequency range 30 kHz to 300 GHz (IARC, 2013a). Exposure occurs in the general population and in occupational settings, with sources including mobile phones, wireless network, television, radio, 5G technologies, Bluetooth, microwaves, cooking hobs, industrial heating of materials, radar, anti-theft devices, and MRI (IARC, 2013a). Exposure to mobile phones is ubiquitous, considering that nearly 95% of the population in high-income countries and 49% in low-income countries own a mobile phone (International Telecommunications Union, 2022). Source-exposure matrices for the general population and workers are available (Vila et al., 2016; van Wel et al., 2021).

Cancer in humans

The 2019 Advisory Group report (IARC, 2019a) indicated that results from epidemiological studies published after IARC Monographs Volume 102 were mixed (Benson et al., 2013; Hardell et al., 2013; Coureau et al., 2014; IARC, 2019a; Röösli et al., 2019). Since the 2019 Advisory Group report (IARC, 2019a), results from the MOBI-Kids study, an international study of brain cancer and the use of EMF technology by children and adolescents (Castaño-Vinyals et al., 2022), the update of the UK Million Women Study (Schüz et al., 2022), and the European Cohort Study of Mobile Phone Use and Health (COSMOS) (Feychting et al., 2024) were published. No increased risk of neuroepithelial brain tumour was found in the MOBI-Kids study (Castaño-Vinyals et al., 2022). In the Million Women Study update, the increased risk for acoustic neuroma reported previously (10+ years use versus never, RR, 2.46; 95% CI, 1.07–5.64) (Benson et al., 2013) was attenuated (10+ years use versus never, RR, 1.32; 95% CI, 0.89–1.96), and no increased risk was found for other cancer subtypes (glioma, glioblastoma, pituitary, eye tumour); however, the exposure assessment was crude. The previous analysis (Benson et al., 2013) reported Ptrend = 0.03 for acoustic neuroma by duration of use, but such an analysis was not reported in the updated publication (Schüz et al., 2022). COSMOS followed 264 574 participants for a median of 7.12 years (recruitment, 2007–2012, in Denmark, Finland, the Netherlands, Sweden, and the UK). For 100 regression-calibrated cumulative hours of calls (country-specific regression-calibrated estimates based on data collected from operators were applied to the self-reported measurements), HRs were 1.00 (95% CI, 0.98–1.02) for glioma, 1.01 (95% CI, 0.96–1.06) for meningioma, and 1.02 (95% CI, 0.99–1.06) for acoustic neuroma (Feychting et al., 2024).

Mobile phone use was associated with increases in overall cancer and NMSC, urinary cancer (in men only), prostate cancer, and vulva cancer, but not brain cancer, in the UK Biobank cohort (Zhang et al., 2024). There was also a significant trend by length of use for NMSC and prostate cancer (Zhang et al., 2024) Concern exists over exposure misclassification, as mobile phone use was captured only at baseline. These findings are not consistent with those of a Danish nationwide cohort study (Schüz et al., 2006).

In IARC Monographs Volume 102 (IARC, 2013a), selection bias and recall bias from case–control studies were noted as being of major concern. Bias analysis available at the time of that evaluation showed that the J-shaped response curve observed in the Interphone study, the largest case–control study on mobile phone use contributing to the evidence published in IARC Monographs Volume 102 (IARC, 2013a), could have been explained by selection bias, leading to underrepresentation of unexposed controls (Vrijheid et al., 2009a). A recent bias analysis using Monte Carlo simulations showed that the J-shaped relation observed in the Interphone study was compatible with a scenario of greater systematic (> 10%) and random error in cases compared with controls, in the absence of any effect (Bouaoun et al., 2024). Validation studies within the Interphone study showed that there was little differential exposure misclassification between cases and controls; however, in heavy users, overestimation was greater in cases than in controls (Vrijheid et al., 2009b).

Cancer in experimental animals

The 2019 Advisory Group report (IARC, 2019a) noted the availability of new data from the large US NTP study that show clear evidence of an increased incidence of malignant schwannoma in the heart (and possibly some evidence of malignant glioma in the brain) in male rats exposed to radiofrequency radiation at frequencies used by mobile phones; however, no clear increased risk was seen in female rats. Some equivocal evidence was observed of increased evidence of malignant glioma in the brain, malignant schwannoma in the heart, and pheochromocytoma in the adrenal medulla (NTP, 2018a, b). An increased risk of schwannoma of the heart observed in male rats exposed to the highest dose was found in an experimental study conducted at the Ramazzini Institute (Falcioni et al., 2018). International studies, aimed to verify the NTP studies, are ongoing in Japan and the Republic of Korea and are expected in 2024 (Ahn et al., 2022). Currently, a systematic review of the effects of RF-EMF on cancer laboratory animals is ongoing as part of a WHO risk assessment project (Mevissen et al., 2022).

Mechanistic evidence

As noted in the 2019 Advisory Group report (IARC, 2019a): “The previous IARC evaluation concluded that there was weak evidence that radiofrequency radiation was genotoxic but that there was no evidence for mutagenicity (IARC, 2013a).” Since then, there have been many new publications on the genotoxicity of RF-EMF radiation, including studies in exposed humans. The formation of micronuclei on buccal mucosal cells was shown in several studies on mobile phone-emitted radiation (Rashmi et al., 2020; Revanth et al., 2020). Other studies found no evidence of micronucleus formation (de Oliveira et al., 2017) or no conclusive evidence for induction of DNA damage or for alterations of the DNA repair capacity in human cells exposed to several frequencies of RF-EMF radiation (Schuermann et al., 2020). In other studies, no effects of RF-EMF exposure on oxidant or antioxidant capacity, apoptosis, or mutations in the TP53 gene were revealed, regardless of the frequency (Khalil et al., 2014; Gulati et al., 2020). The authors of a meta-analysis to investigate whether RF-EMF emitted by mobile phones have genotoxic or cytotoxic effects on the oral epithelium concluded that the evidence for genotoxic effects was weak (Dos Santos et al., 2020). In experimental systems, there is a large body of literature on investigations of the genotoxicity of RF-EMF (Meltz, 2003). A study showed that rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas, and rat cardiac schwannomas also harbour mutations in some of the queried cancer genes (Brooks et al., 2024). An independent systematic review of the genotoxicity of RF-EMF in in vitro mammalian models is ongoing (Romeo et al., 2021).

In addition, evidence associated with other KCs is available. For example, chronic exposure to RF-EMF emitted from mobile phones may induce oxidative stress and an inflammatory response in rats (Singh et al., 2020). Currently, a systematic review of the effects of RF-EMF on biomarkers of oxidative stress in vivo and in vitro is ongoing as part of the WHO risk assessment project (Henschenmacher et al., 2022). Several studies have investigated the immunotoxicity of RF-EMF (Yadav et al., 2022). Mobile phone radiofrequency radiation was found to be associated with thyroid gland insufficiency and alterations in serum thyroid hormone levels in exposed humans and in rodents, with a possible disruption in the hypothalamic–pituitary–thyroid axis (Alkayyali et al., 2021).

Summary

Since the last evaluation, there have been several new high-quality studies. Overall, the human cancer evidence is mixed. There is new evidence of carcinogenicity in experimental animals. Since the previous evaluation, there is new mechanistic evidence related to the KCs, especially genotoxicity in experimental systems and in exposed humans. However, several of the genotoxicity studies in exposed humans provided inconsistent results. Thus, the mechanistic available evidence currently available may be inconclusive.

Overall, the new evidence regarding cancer in humans and in experimental animals could support a re-evaluation, although a change in the current classification of the carcinogenicity of RF-EMF is uncertain. The Advisory Group therefore considered an IARC Monographs evaluation of RF-EMF to be warranted but suggests an evaluation in the latter half of the next 5 years, to await the results of ongoing cancer bioassays, which may provide additional mechanistic evidence.

Recommendation: High priority (and ready for evaluation within 5 years)

Open access report: https://www.iarc.who.int/news-events/advisory-group-recommendations-on-priorities-for-the-iarc-monographs-during-2025-2029/