Risk in the call

A World Health Organisation agency evaluates electromagnetic radiation from mobile phones for carcinogenicity.

THERE has been a dramatic increase in the use of the mobile phone worldwide since its introduction in the mid-1980s. According to the estimate of the International Telecommunications Union (ITU), currently there are about five billion mobile phone subscribers globally.

In the past decade or so, there has been growing concern about the possibility of adverse health effects, particularly brain cancer, resulting from exposure to radiofrequency electromagnetic fields (RF-EMF), such as those emitted by wireless communication devices ( Frontline, May 9, 2008). On May 31, the World Health Organisation's (WHO) International Agency for Research on Cancer (IARC) classified RF-EMF as a possible cancer-causing agent in the case of humans, under Group 2B of its classification system of carcinogens. This is based on its assessment that wireless phone use causes an increased risk for glioma, a malignant type of brain cancer. The decision to classify RF-EMF as a possible carcinogenic was taken by the IARC's Working Group at a meeting held in Lyon, France, from May 24 to 31. The meeting was organised to assess the potential hazards from exposure to RF-EMF. The group comprised 30 scientists from 14 countries, and its evaluation will be published as Volume 102 of IARC Monographs.

Mobile phones emit non-ionising radiation, which, unlike X-rays or gamma rays, does not strip electrons away from molecules (ionise) in cell tissue and thus cannot damage deoxyribonucleic acid (DNA) and other biomolecules. The energy of mobile phone radiation is, in fact, a million times smaller than the energy required to break a chemical bond and cause chemical reactions. However, RF-EMF can cause heating of the material on which it deposits its tiny energy and at high enough levels can damage the cell tissue by thermal effect. In the late 1990s, this resulted in the United States' Federal Communications Commission (FCC) and the International Commission on Non-Ionising Radiation Protection (ICNIRP) in Europe to set limits on the emitting power of mobile phones in terms of what is called the specific absorption rate (SAR), a measure of the energy deposited in biological systems.

SAR is defined in watts/kg and is the rate of absorption of electromagnetic energy in a unit mass of tissue. The limits set by the FCC and the ICNIRP were 1.6 W/kg and 2 W/kg respectively. Also, it was first demonstrated by the Finnish research team led by Dariusz Leszczynski of STUK, the Finnish Radiation and Nuclear Safety Authority, that protein expression in cells could be altered by RF-EMF through non-thermal effects ( Frontline, May 9, 2008). The question is whether these standards are sufficient to protect against health effects owing to long-term exposures. Neither the FCC nor the ICNIRP has recommended any changes in their present standards on the basis of the scientific evidence of the adverse effects of RF-EMF available so far. It remains to be seen how these agencies interpret the IARC's conclusions and act on them.

This is the first time that the IARC has evaluated electromagnetic radiation from mobile phone use for carcinogenicity. Until now, WHO had relied on the evaluations done by the ICNIRP. The ICNIRP has held that there is no link between mobile phone use and cancer and that any such link is unlikely. Of the 30 members of the IARC Working Group, 27 participated in the voting, and as per reports, there was a clear and overwhelming majority in favour of the 2B classification. Interestingly, the Working Group participants have been apparently told not to disclose the voting pattern.

The IARC's classification is guided by epidemiological and experimental evidence of carcinogenicity and mechanistic (relating to the biological mechanism of the agent) and other relevant data such as exposure. While Group 2A includes 59 agents that are probably carcinogenic, Group 2B has 266 agents, including coffee, occupational exposure during dry cleaning and firefighting, marine diesel fuel, styrene and even pickled vegetables, that are possibly carcinogenic. According to the IARC, the terms have no quantitative significance and are used simply as descriptors of different levels of evidencewith probably carcinogenic signifying a higher level of evidence.

More precisely, the IARC labels an agent as possibly carcinogenic to humans when there is limited evidence of carcinogenicity in humans and there is less than sufficient evidence of carcinogenicity in experimental animals. The evidence of carcinogenicity is considered sufficient if there is an established causal relationship between exposure to the agent and human cancer. The evidence is considered limited if only a positive association has been observed for which a causal interpretation is credible but chance, bias or confounding could not be ruled out with reasonable confidence.

The label 2B may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in animals. The evidence is considered inadequate if the available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association between exposure and cancer, or if no data on human cancer are available.

In some instances, an agent for which there is inadequate evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in animals together with supporting evidence from mechanistic and other relevant data is placed in this category. An agent may also be so categorised solely on the basis of strong evidence from mechanistic and other relevant data.

In the present case, overall, the available evidence was evaluated as being limited for glioma and acoustic neuroma (a slow-growing benign tumour of the nerve that connects the ear to the brain), and inadequate for other types of cancers, according to the IARC press release. The evidence from occupational and environmental exposures to RF-EMF was similarly stated to be inadequate.

In response to an e-mail query as to which of the (four) criteria dictated the inclusion of RF-EMF in Group 2B, Elisabeth Cardis, a member of the IARC Working Group, merely stated that a summary of the evaluation and the basis for the classification would be published in the journal Lancet Oncology online and in print in its July issue. However, according to Leszczynski, a member of the Working Group whose study in 2008 is perhaps the only mechanistic study of the effects of RF-EMF in human volunteers, limited evidence of carcinogenicity both in humans and animals was the criterion used by the IARC to include RF-EMF in Group 2B. This implies that there probably was supporting evidence from mechanistic and/or exposure data. Clearly, one has to await the publication of the results for details and clarity on the issue.

The pertinent question then is, what does an average mobile phone user or even policymakers make of these technicalities to protect himself/herself or the nation's population from the adverse effects of mobile phone use? Is its potential carcinogenicity just as much as that from drinking coffee?

The statements of the IARC are not very helpful in answering these questions. Significantly, the IARC has not quantified the risk. However, as an indicator of the quantified risk, the IARC has quoted from the results of the Interphone study of past mobile phone use (up to 2004) that were published in 2010. This is the largest epidemiological (case-control) study on the issue to date. One of the findings of the study, which involved 21 scientists from 13 countries and was coordinated by the IARC, was that there was a 40 per cent increased risk for gliomas in the highest category (top decile) of heavy users (call duration of 30 min a day over a 10-year period).

Jonathan Samet, the Chairman of the Working Group, was quoted in the IARC release as saying that the evidence, while still accumulating, is strong enough to support a conclusion and the 2B classification. The conclusion means that there could be some risk, and, therefore, we need to keep a close watch for a link between cell phones and cancer risk. The mandate of the IARC monograph is to evaluate whether agents in our environment might increase the risk of cancer. [I]t isup to national health agencies to evaluate potential risks and benefits and to use this information as scientific support for their actions to prevent exposure to potential carcinogens, Elisabeth Cardis said.

Christopher Wild, the IARC Director, on the other hand, said: Given the potential consequences for public health of this classification and findings, it is important that additional research be conducted into the long-term heavy use of mobile phones. Pending the availability of such information, it is important to take pragmatic measures to reduce exposure, such as hands-free devices or texting.

Of course, it is also known that exposure is reduced by limiting the number and length of calls, and by using the phone in areas of good reception, which allows the phone to transmit at reduced power. Also, RF radiation falls off quickly, and the farther one keeps the phone from the body, the less will be the exposure.

The Mobile Manufacturers Forum (MMF) has given its own interpretation to the IARC pronouncement. It said in a release: It is significant that IARC has concluded that RF-EMF is not a definite or a probable carcinogen. Rather, IARC has only concluded that it may still be possible that RF fields are carcinogenic. IARC has only assessed the possibility of risk, not the likelihood of risk in normal use. To confuse matters further, the MMF added that wireless communication equipment is designed to operate within international and national exposure limits, which have substantial margins built into them.

As Leszczynski pointed out in his blog, the last statement of the MMF misses the point that epidemiological evidence (notwithstanding its quality) has been gathered in studies where study subjects used these, safety limits fulfilling, wireless communication equipment[.] Equipment, we are being assured, is safe because it complies with the current safety standards. Logic of MMF explanation escapes me. I am not suggesting that, following IARC evaluation, the current safety limits should automatically be changed. Safety limits are what they are and they protect users from some effects of mobile phone radiation. Whether they protect us from all effects, we do not know and that is why IARC-evaluation-provided-stimulus-for-research should help to get an answer.

EVALUATION OF HAZARD

Pending the publication of the details, what is unsettling about the current evaluation of the potential hazard of RF-EMF is that if one goes by the IARC press release, it seems to be anchored around the first results of the Interphone study published in May 2010. However, it is pertinent to point out here that the Interphone study drew widespread criticism over its flawed methodology when the paper was published. This interview-based case-control study was initiated in 2000 at a cost of about 20 million and included the largest number of users with at least 10 years of exposure. Interestingly, 5.5 million of this came from industry sources, the MMF and the GSM Association. According to the IARC, the funding was through a firewall mechanism to guarantee the independence of the scientists.

The study focussed on four types of tumours in tissues that absorb RF energy emitted by mobile phones to the greatest extent. The first paper from the study had reported the results of analyses of brain tumour risk in relation to mobile phone use. The subjects included 2,708 glioma and 2,409 meningioma (tumours of the tissue that surrounds the brain) patients and matched controls conducted in the participating countries using a common protocol. The interpretation of the results and the language used in the article for the description of the final result were convoluted as if somewhat designed to satisfy everyone those expecting no effect and those expecting an effect, Leszczynski wrote in his blog.

Overall, said the paper in conclusion, no increase in risk in glioma or meningioma was observed with the use of mobile phones. There were suggestions of an increased risk of glioma at the highest exposure levels but biases and error prevent a causal interpretation. The possible effects of long-term heavy use of mobile phones require further investigation. But even this conclusion was problematic because of flaws in the methodology used, which even the scientists of the study recognised. Although the study had very good data on tumour and cancer histories of the patients, it had suspect data on cellphone usage.

According to Leszczynski, inherent to all case-control studies on the health effects of mobile phone use is the insufficient quality of dosimetry, selection and misclassification bias, and low sensitivity in detection of health risk. Drawing any health-related conclusions is like flipping a coin, he blogged. In the Interphone study, there were apparently many exceptions from the common protocol. Further, it defined a regular user as one who makes at least one call a week for the period of at least six months. This meant that the category of regular users included occasional users and those who used it frequently, say 25 calls a day. As Leszczynski pointed out, if we assumed that heavy exposure caused health effects, then these effects would be diluted by the inclusion of subjects with low exposure in the same group.

A MAJOR PROBLEM

The other major problem in this interview-based study was the participants' recall ability of the extent of their cellphone usage over the past 10 years. Also, in the early part of the period covered by the study, network providers did not provide subscribers' usage data. The matching of controls with patients was also problematic. The issue was whether the control group should include only those who never used a cellphone or include those who used it infrequently as well. Such selection bias could affect the statistical analyses of data significantly.

The analysis using the first group, in fact, showed the somewhat puzzling result that regular users of mobile phones had a reduced risk of developing glioma! This, as the ICNIRP has noted, is likely to be a methodological artefact. Results of analyses of subgroups showed both increased risks and decreased risks with respect to the lobe of the brain and to the side of use. Interestingly, the May 2010 paper does not mention this in its conclusion.

Further complication in evaluating the risk of cancer from mobile phone usage arises from the fact that the technology is of recent origin. Brain tumours, on the other hand, have a long latency period, which ranges from 10 to 20 years. The study, however, had very few people who have been mobile users for over 10 years. This makes the conclusion statistically unreliable.

At the time of the publication of the first results from the study, the IARC Director, said: Increased risk of brain cancer is not established from the data from Interphone. However, observations at the highest level of cumulative call time and the changing patterns of mobile phone use since the period studied by Interphone [that is, after 2004], particularly in young people, mean that further investigation of mobile phone use and brain cancer risk is merited.

Elisabeth Cardis, who is also the principal investigator of the Interphone study, had then stated: The Interphone study will continue with additional analyses of mobile phone use and tumours of the acoustic nerve and parotid gland.

In sum, until a year ago, the verdict on the carcinogenicity of mobile phone radiation was at best equivocal. In spite of several studies worldwide, including this largest case-control study since 2000, there was, as a Yale University in-house journal put it, precious little certainty over whether cellphones pose any danger to those using them. For nearly every study that reports an effect, another, just as carefully conducted, finds none.

The question obviously is what has changed during the intervening one-year period that led the IARC to make a more definitive assessment of the risk after its comprehensive review of the issue in May 2011?

Elisabeth Cardis said that the evaluation meeting not only reviewed the first results from the international analyses of the Interphone study but also from all available evidence, including a number of other manuscripts currently in press from the Interphone study, results of other epidemiological studies and of experiments. This is the first time that the IARC has made an evaluation of the carcinogenicity of RF and the meeting had been scheduled to ensure that results of important ongoing studies [epidemiological and experimental] would be available for review by the Working Group before it met, she added.

As regards epidemiological evidence, apparently the IARC's Epidemiology Group concluded that the results of three studies by the Swedish cancer specialist Lennart Hardell (1999, 2002 and 2005) and the results of the Interphone study (2010) provided enough evidence of the possibility of an effect. Hardell's studies had included more patients who had used cellphones for 10 years or longer and, unlike Interphone, were performed without financial support from the wireless industry. The findings suggested that the more hours of mobile phone use over time, the higher the risk of developing brain tumours. The risk also increased with the power emitted from the wireless device, years since first use, total exposure, and younger age of first wireless phone use.

In an e-mail response, Leszczynski, who had termed the results of the Interphone study as scientifically unreliable and non-informative because of its design flaws, said, I still stand behind every criticism of epidemiological studies that I expressed in my blog[s]. However, the IARC evaluation was not only based on epidemiological studies but also on animal studies and mechanistic studies. So, my vote for 2B was based on data from all three areas of evidence, and not only on epidemiology.

The situation in India which was not one of the 13 countries in the Interphone study, as in 2000 the use of mobile phones was not as widespread in the country as now with regard to mobile phone radiation standards for safe protection seems to be worse than in most parts of the world. WHO has a webpage that gives details of safety standards for RF usage in all countries. The relevant columns for mobile phones against India in this WHO database are blank. Though the regulations of the Department of Telecommunications (DoT) require that devices meet the ICNIRP SAR value standard of 2 W/kg, apparently there is no independent technical agency to monitor whether manufacturers comply with it. The manufacturer's declaration is taken at face value.

As Leszczynski points out, even assuming that mobile firms comply with the regulations, the present SAR standards do not necessarily take into account how people actually use mobile phones. While our heads may be exposed to RF radiation within the allowed limits, our bodies and skin may be getting more than the phone's advertised dose. A hands-free set may reduce exposure to the brain, but the body may still be exposed if one keeps the phone in the shirt pocket.

In November 2010, an inter-ministerial committee constituted by the DoT drew up guidelines for RF-EMF usage in the country. It has recommended following the FCC standard of 1.6 W/kg SAR and a 10 per cent reduction in the RF emission from transmitting towers from the present value of 9.2 W/m {+2}.

In June 2010, after the publication of the first Interphone study results, the Indian Council of Medical Research (ICMR) initiated a prospective cohort study that is to include 4,500 subjects in Delhi and its surrounding areas over a five-year period. According to R.S. Sharma of the ICMR, phase-I of this study will evaluate whether mobile phone use has any relationship with neurological, reproductive, cardiovascular and ear-nose-throat disorders. Now that the IARC has notified RF-EMF as a possible carcinogen, phase-II of the study, according to him, will include cancer as well.

As long as the health risk from mobile phone use remains uncertain, notwithstanding the IARC's classification of RF-EMF as a possible carcinogen, the prudent approach is to follow the precautionary principle of reducing the exposure as best as one can.