The world's high background natural radiation areas (HBNRAs) revisited: A broad overview of the dosimetric, epidemiological and radiobiological issues

Radiation Measurements 73 (2015) 51e59

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Review

The world's high background natural radiation areas (HBNRAs) revisited: A broad overview of the dosimetric, epidemiological and radiobiological issues Abubakar Sadiq Aliyu a, b, *, Ahmad Termizi Ramli a a b

Department of Physics, Universiti Teknologi Malaysia, UTM Skudai, 81310 Johor, Malaysia Department of Physics, Nasarawa State University Keffi, Nigeria

h i g h l i g h t s
Some of the challenging issues of HBNRAs have not been resolved.
A literature review of the most recent studies of HBNRAs has been conducted.
An overview of some of the challenging issues and viable solutions are presented.

a r t i c l e i n f o

a b s t r a c t

Article history: Received 9 May 2014 Received in revised form 8 December 2014 Accepted 10 January 2015 Available online 10 January 2015

The residents of the world's high background natural radiation areas (HBNRAs), such as Ramsar (in Iran), Guarapari (in Brazil), Orissa and Kerala (in India) and Yangjiang (in China) have lived in these areas for generations under extraordinary radiation fields. The failure of earlier epidemiological studies to report any substantial increase in cancer incidence in HBNRAs has raised some controversy regarding the validity of the linear no-threshold hypothesis. This paper reviews some of the most recent studies of HBNRAs with the intent of stimulating greater research interest in the dosimetric, epidemiological and radiobiological issues related to the world's HBNRAs and proposes solutions to the challenges facing HBNRA studies. This paper may serve as a useful reference for some of the harder-to-find literature. © 2015 Elsevier Ltd. All rights reserved.

Keywords: High background natural radiation areas (HBNRAs) Ramsar Guarapari Kerala Yangjiang Cancer epidemiology Chromosomal aberration Dosimetry

1. Introduction Life began in a radiation field that is more intense than that of today (Mortazavi, 2012); the radiation level today is ten-fold lower than that during the Precambrian era (Karam and Leslie, 2005; Møller and Mousseau, 2013). One of the radionuclides in man's environment that contributes a large proportion of the radiation dose to the population is radon (Bavarnegin et al., 2013). Nearly

* Corresponding author. Department of Physics, Universiti Teknologi Malaysia, UTM Skudai, 81310 Johor, Malaysia. E-mail addresses: [email protected], [email protected] (A.S. Aliyu). http://dx.doi.org/10.1016/j.radmeas.2015.01.007 1350-4487/© 2015 Elsevier Ltd. All rights reserved.

eighty percent of the annual effective dose attributed to radiation exposure originates from background natural radiation, which is predominantly produced by cosmogenic and primordial radionuclides (Schnelzer et al., 2010). Inhabitants of the world's HBNRAs and radon prone areas receive radiation doses that are relatively higher than the doses in the normal background radiation areas (NBRAs) (Sohrabi, 2013a,b). Some of the world's HBNRAs are found in Kerala (India), Guarapari (Brazil), Yangjiang (China), and Ramsar (Iran), a northern coastal city in Iran (Mortazavi et al., 2002; Mortazavi and Mozdarani, 2012). Based on the inhabitants' annual effective dose (HE), Sohrabi (2013a) has classified the world's HBNRAs as follows: low

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(HE ¼ 5 mSv y1), medium (HE ¼ 5e10 mSv y1), high (HE ¼ 20e50 mSv y1) and very high (HE > 50 mSv y1). This classification is based on the dose limits of the ICRP and the 2.4 mSv y1 global mean dose value reported by UNSCEAR (ICRP, 1991; 2007; UNSCEAR, 2000a,b). The specific characteristics of HBNRAs depend on the stability of the natural radioactivity. There are areas in which the radiation dose is constant over time and other areas in which the dose varies with time (Sohrabi, 2013a). The failure of earlier epidemiological studies to report any substantial increase in cancer incidence in the HBNRAs has raised some controversy regarding the validity of the linear no-threshold (LNT) hypothesis. Hence, a scrutiny of the current literature that presents a broad overview of the major issues and proposes viable solutions to the greatest challenges is timely and relevant. A number of excellent studies and reviews have been conducted regarding the radiological issues related to HBNRAs. For instance, Sohrabi (1998) reviewed the literature concerning the sources of naturally occurring radioactive material (NORM) and human exposure and has presented criteria for the classification of HBNRAs. These classifications are presented in the author's recent paper, which considers the health implications in Ramsar and the need to protect the Ramsar residents from radiation (Sohrabi, 2013a). In their study, on of the lessons learned regarding health risks as a result of human exposure to elevated levels of background radiation, Hendry et al. (2009) note that there is an established association between long-term radiation exposure in the general population and disease incidence in radon-prone areas. However, these authors also observed that studies in non-radon HBNRAs are based on ecological design and provide little information. The authors recommend the monitoring of environmental dose rates and the establishment of a database in which the individual dose estimates for residents can be recorded; these dose estimates should be based on retrospective internal and external dosimetry. The authors also recommend that data concerning the effects of nonradiation clastogens should also be collected because these effects have produced a confounding effect in a Chinese study conducted by Hayata et al. (2004) involving a large sample size, in which the effects of low levels of radiation on chromosomes were concealed. Møller and Mousseau (2013) have assessed the effects of variations in background radioactivity on humans, animals and other organisms. The authors expected that the hormetic effects of radiation should be more pronounced in HBNRAs because of adaptation to such enhanced levels of radiation; they also predicted that exposure to natural radiation should have positive effects on humans and other organisms if hormesis operates at naturally occurring low doses of radiation. However, the results of the metaanalysis were inconsistent with the general hypothesis of hormesis related to low levels of natural background radiation; instead, the authors observed generally negative effects of radiation on mutations, immunology and life history. The results of Møller and Mousseau (2013) support the argument of Mossman (2001) regarding the “deconstruction of radiation hormesis,” namely, that data purported to support radiation hormesis in human populations is deficient and based on epidemiological findings and that evidence of hormetic effects is weak and inconsistent. In an alternative opinion, (Doss, 2014) argued that in the early 1980s, radiation hormesis was proposed to reduce the incidence of cancers, but scientists have failed to investigate hormetic effects in human. The current study has no intention of summarizing all the various controversial arguments for or against the LNT model; it is, however, important to investigate of radiation hormesis in humans. The International Conference on High Levels of Natural Radiation and Radon Areas (ICHLNRRA) conference is held every four years. This serves as the largest gathering at which researchers

interested in the HBNRAs convene to share knowledge. The most recent was the 8th ICHLNRRA, which was held on 1e5 September 2014 at Czech Technical University. Some ICHLNRRA conferences that have been held in the past include Brazil (1977), India (1981), Iran (1990), China (1996), Germany (2000), Japan (2004) and India (2010). The proceedings of the 3rd, 4th 5th and 6th ICHLNRRA conferences are available through Science Direct (Sohrabi et al., 1993; Wei et al., 1997; Burkart et al., 2002; Sugahara et al., 2005). This paper reviews some of the most recent studies of HBNRAs with the intent of stimulating greater research interest in the dosimetric, epidemiological and radiobiological issues related to HBNRAs. 2. The world HBNRAs considered 2.1. Yangjiang (China) In China, the Yangjiang area in Guangdong province is a known HBNRA. Most of its residents have lived there for over 5 generations (Tao et al., 2000a). The average annual dose of external radiation from natural sources, including thorium, in this HBNRA has been estimated to be 3.5 mSv y1 (Zou et al., 2005). The primary source of the elevated level of radiation is monazite that contains 232Th, 238 U, and 4K. The average annual internal effective dose received by the inhabitants from natural sources of exposures in the HBNRAs of Yangjiang has been estimated to be 4.27 mSv (Zou et al., 2005). A health survey of the inhabitants of the HBNRAs of Yangjiang, China, was conducted over a span of two decades, and the results are available in literature (Hayata et al., 2000, 2004; Sun and Carr, 2005; Tao et al., 2000b; Wang et al., 1990; Wei and Sugahara, 2000; Zhang et al., 2003, 2004, 2008; 2010; Zou et al., 2000). Wang et al. (1990) have studied thyroid nodularity caused by chronic radiation exposure in Yangjiang's female residents aged 50e56 years. The authors compared their results with those obtained from women of the same age group who were exposed to normal background radiation. The cumulative dose to the thyroid in the HBNRA residents was two-fold higher than that of the residents of the NBRAs. However, the prevalence of nodular diseases in the two groups of residents was comparable. A higher prevalence of mild diffuse goiter was observed in the HBNRA residents, and this was attributed to their low iodine consumption. The study concluded that a lifetime exposure to low-level radiation does not result in any discernible increase in thyroid nodularity in the investigated HBNRA. However, such exposure may cause chromosomal damage. An interesting feature of the work of Wang et al. is its ability to consider the influence of diet. Other issues that could be considered to be limitations of this study are the small sample size and the consideration of only female residents. However, this work paved the way for further radiobiological studies of the HBNRA residents. With the objective of studying the health effects of long-term exposure to low-level radiation, Hayata et al. (2004) analyzed the chromosomes of peripheral lymphocytes from the residents of HBNRAs in Yangjiang and compared their results with those obtained from control areas with normal background radiation. The authors found an increase in the frequency of dicentric and ring chromosome aberrations in the HBNRA residents. In an earlier study, Hayata et al. (2000) used chromosome painting analysis to measure the effects of chronic exposure in 9 HBNRA residents and 8 NBRA residents. Dose effects were detected in dicentrics, and the frequency of translocation varied among adults. The study found no statistically significant increase in the frequency of chromosome aberration in the HBNRA residents. An epidemiological study of cancer incidence among residents of Yangjiang was conducted by Zou et al. (2005). This study observed no significant difference in cancer-related mortality rates

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Table 1 Effects of chronic exposure to radiation of residents in Yangjiang, China. HBNRA Country

Yangjiang China

Chromosomal aberrations

Cancer data: type (ref.)

Reference

Findings

Reference

Findings

(Wang et al., 1990)

[

4

(Chen and Wei, 1991) (Tao et al., 2000a) (Hayata et al., 2004) (Zhang et al., 2003, 2004) (Hayata et al., 2000) (Zhang et al., 2010)

[ [ [ 4 4 (Adaptive response)

All-cancer mortality (Chen and Wei, 1991; Wei and Sugahara, 2000; Wei et al., 1990; Tao et al., 2000a) Leukemia mortality (UNSCEAR, 2000a)

Y

Notes: The symbols [ or Y refer to whether the cited study reported a significant increase or decrease, respectively, in the average frequency of chromosome aberrations per cell or in the incidence of cancer with respect to that in the controls from areas with a normal radiation background. The symbol 4 denotes a lack of any significant difference.

between the HBNRA and the NBRA residents. Excess mortality related to esophageal cancer was observed in the HBNRA residents, but it did not exhibit a monotonic increase with increasing external radiation dose or with increasing cumulative lifetime dose. This excess mortality was observed in the younger generation and may have been related to changes in their lifestyle (Sun and Carr, 2005). The results of some of the recent studies on chromosome aberration and cancer data in Yangjiang residents are summarized in Table 1. For Yangjiang residents, it has been demonstrated in Table 1 that the mortality rates from all cancers and those from leukemia, breast and lung cancers were no higher than those for residents of the control area. Furthermore, when samples of circulating lymphocytes drawn from the inhabitants were tested in vitro for their mitotic response to phytohemagglutinin (PHA) and their degree of unscheduled DNA synthesis (UDS), higher responsiveness and UDS rates were observed in the HBNRA samples than in those from the NBRAs (Chen and Wei, 1991). Wei et al. (1990) noted that for all the HBNRA residents, the cancer (non-leukemia) mortality was 14.6% lower than that for NBRA residents; the leukemia mortality among men was 15% and 60% lower among men and women respectively. No difference in the frequency of various genetic diseases was observed between the HBNRA and the NBRA. To date, based on published data, the cancer mortality in Chinese HBNRAs has been found to be either lower than that in the control area (Wei et al., 1990) or to exhibit no statistically significant difference (Tao et al., 2000a,b). In a later study, Zhang et al. (2010) introduced the concept of adaptive response to describe the resistance observed in cultured human lymphocytes from the HBNRAs of China. It is important to note that most of these cancer epidemiological studies rely on scant data, and a more robust methodology is needed to reach a reliable conclusion. A high incidence of Down's syndrome was also observed in the Chinese HBNRA (Wei et al., 1990). A major factor that was found to influence the prevalence of Down's syndrome by the authors was the difference in the age of maternity between the HBNRA and NBRA mothers, which resulted in an extremely low frequency of

Down's syndrome in the NBRA because the chances of having a baby with Down's syndrome are higher for older mothers. This analysis demonstrates that factors other than the exposure to high background radiation may have influenced the results of Kochupillai et al. (1976). 2.2. Kerala, Tamil Nadu and Orissa coasts (India) The Kerala, Tamil Nadu, and Orissa coasts are known HBNRAs in Peninsular India, and these areas have been widely investigated (Chougaonkar et al., 2004; Derin et al., 2012; Dissanayake and Chandrajith, 2009; Mohanty et al., 2004; Narayana et al., 1995; Paul et al., 1998). The high level of natural radiation in these HBRAs is attributed to the abundance of monazite along with other heavy minerals, such as ilmenite, rutile, zircon and garnet, among others. Mohanty et al. (2004) have studied the natural radioactivity level in the high background radiation areas on the Eastern coast of Orissa, India. The measured activity concentrations of primordial radionuclides (232Th, 238U, and 4K) in bulk sand samples were found to be 2825 ± 50, 350 ± 20 and 180 ± 25 Bq kg1, respectively. The absorbed mean gamma dose rates in air attributed to naturally occurring radionuclides was 1925 ± 718 nGy h1, which is over thirty-fold higher than the world average value of 55 nGy h1 (UNSCEAR, 1988). The annual external effective dose rate for the region varied from 0.78 to 3.86 mSv y1, with a mean value of 2.36 ± 0.88 mSv y1. In Kerala, a range of effective dose rate from 0.5 to 15 mSv y1 was reported for some of the residents (Chougaonkar et al., 2004; Derin et al., 2012). Some of the locations in India with the high natural radioactivity include Ullal in Karnataka (Narayana et al., 1995; Radhakrishna et al., 1993) and Kalpakkam in Tamil Nadu (Kannan et al., 2002; Radhakrishna et al., 1993), which are all located in the coastal regions of Peninsular India. From the mid-1960s to the present, a number of radioepidemiological studies have been conducted to assess the health effects of long-term exposure to radiation in the residents of India's HBNRAs (Cheriyan et al., 1999; Das and Karuppasamy, 2009;

Table 2 Effects of chronic exposure to radiation of residents in Kerala, India. HBNRA Country

Kerala, India

Chromosomal aberrations

Cancer data: type (ref.)

Reference

Findings

Reference

Findings

(Kochupillai et al., 1976) (Cheriyan et al., 1999) (Das et al., 2009) (Das and Karuppasamy, 2009)

[ 4 4 4

Thyroid cancer prevalence (Pillai et al., 1976) Oral cancer incidence (Nair et al., 1988) All-cancer incidence (Nair et al., 1999) All-cancer incidence (Nair et al., 2009)

4 [ 4 4

Notes: The symbols [ or Y refer to whether the cited study reported a significant increase or decrease, respectively, in the average frequency of chromosome aberrations per cell or in the incidence of cancer with respect to that in the controls from areas with a normal radiation background. The symbol 4 denotes a lack of any significant difference.

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Krishnan and Vijayalakshmi, 2005; Kochupillai et al., 1976; Nair et al., 1999, 2009; Pillai et al., 1976). A summary of the results of these studies is presented in Table 2. Gruneberg (1966) and Ahuja et al. (1973) have studied the residents in Kerala area with respect to dermatoglyphics and demographic data such as fertility index, sex ratio and infant mortality rate have indicated that no mutational effects were observed. However, in an epidemiological study of nodular lesions of the thyroid in the area, Kochupillai et al. (1976) observed a high incidence of Down's syndrome and other forms of severe mental retardation, and this observation spurred the authors to conduct a house-to-house survey of developmental abnormalities in the HBNRA; and compared their results with those of the NBRAs. Upon comparing their results with evidence of an increased frequency of chromosome aberrations in the HBNRA, the authors espoused the view that radiation-induced genetic anomalies occurred with above-average frequency in the HBNRA residents. Cytogenetic study using cord blood samples from over 8000 and 1700 newborns from HBNRAs of the Kerala coast and NBRAs, respectively was conducted (Cheriyan et al., 1999). The result of this study showed that there was no significant difference between the frequencies of chromosome aberration in the two infants' groups. A smaller sample size of 271 newborns (from both HBNRA and NBRA) was considered by Das and Karuppasamy (2009). Their results also showed that the high level of naturally occurring radiation has no significant effect on the induction of micronuclei frequency among infants. A cytogenetic study using cord blood samples from over 8000 and 1700 newborns from the HBNRAs of the Kerala coast and a NBRA, respectively, has been conducted (Cheriyan et al., 1999). The results of this study indicated that there was no significant difference between the frequencies of chromosome aberration in the two groups of infants. A smaller sample size of 271 newborns (from both the HBNRA and the NBRA) was considered by Das and Karuppasamy (2009). Their results also indicated that a high level of naturally occurring radiation had no significant effect on the induced micronucleus frequency among the infants. Telomere length (TL) is a biomarker for cancer; Das et al. (2009) have measured the TL in 233 and 77 HBNRA and NBRA residents, respectively. The TL was studied among adults (aged 18e40 years) of a mean maternal age of 26.1. A negative correlation was observed between the TL and the age of the residents. This observation led the authors to conclude that the elevated level of background natural radiation had no discernible effect on the TL among the adult residents of HBNRAs on the Kerala coast. Over the past two decades, Nair and co-workers have conducted cancer epidemiological studies in Kerala's HBNRAs (Nair et al., 1988, 1999, 2009). Of these studies, only the earliest demonstrated a significant increase in oral cancer in the HBNRAs. In the latest study (Nair et al., 2009), the authors concluded that the cancer incidence in the HBNRA revealed no high-background-radiation-related excess of malignant tumors. Although the statistical power of the study may not have been adequate because of the low doses, these finding suggests that it is unlikely that estimates of cancer risk at low doses are substantially greater than currently believed. It is important to note that factors such as bias and confounding may affect the outcomes of these epidemiological studies. In an attempt to provide better solutions to some of the problems associated with bioepidemiology in HBNRAs, a recent study of the biological effects of long-term exposure to elevated levels of natural radioactivity in Ramsar by Taeb et al. (2014) considered 8 tumor markers in human blood serum. The results of this study are discussed in a later part of this paper. The observed increase in the frequency of chromosome aberration and the lack of cancer prevalence in the HBNRAs of Kerala

(Table 2) have been cited to support the argument that chromosomal aberration is not a specific biomarker for radiation carcinogenesis (Abdollahi, 2013; Hendry et al., 2009). However, before accepting this generalization, it is important to emphasize that most (if not all) of the cancer studies in these HBNRAs were based on epidemiological studies, which are affected by factors such as bias and confounding. Therefore, more stringent techniques should be adopted to address this challenging issue. Kendall (2005) has proposed ecological design as a superior technique for addressing these limitations. Hart (2011) has noted that ecological design is a valid technique for revealing doseeresponse relationships, but its major weakness is that it is based on grouped data rather than individual data: drawing conclusions regarding individuals based on group-sampling studies can be misleading and may result in an erroneous interpretation known as an “ecological fallacy” (Cohen, 1990; DeAngelis, 1990). Various methods have been developed to reduce ecological fallacy (Salway and Wakefield, 2008; Wakefield and Shaddick, 2006). 2.3. HBNRAs in Brazil The HBNRAs in Brazil are in Poços de Caldas, Arax'a, and Tapira, which are in volcanic alkaline intrusive zone in the Minas Gerais State, as well as Guarapari, located in the Espirito Santo State on the Atlantic Coast. According to Hendry et al. (2009), six thousand persons reside in the HBNRAs in Poços de Caldas, 1300 in Arax'a, and 12,000 in Guarapari. In some of Brazil's HBNRAs, monazite sand deposits are abundant on certain black sand beaches. The external radiation levels on these black sand beaches reach as high as 50 mGy h1. The minerals that are present in abundance in these coastal regions of Brazil are monazite, rutile, ilmenite, zircon, cassiterite, thorianite, pyrochlore and niobate-tantalite. Analyses of the mineral contents of beach sand have demonstrated that monazite from beach sand contains up to 39% cerium oxide (CeO2), 16% lanthanum oxide (La2O3), 14% neodymium oxide (Nd2O3), 5% yttrium, 6% thorium dioxide (ThO2) and 0.31% uranium oxide and phosphates (Dissanayake and Chandrajith, 2009). An abnormally high natural radium concentration in the surface waters has been reported in a coastal lagoon close to a monazite sand separation plant in the Buena Lagoon region in the state of Rio de Janeiro in Brazil (Lauria and Godoy, 2002). The authors (Laria and Godoy) had earlier suggested that the high level of 228Ra (2 Bq L1) was attributable to mineral processing activities in which the coastal water was used as process water. A more detailed investigation by the same authors revealed that the abnormal radium concentrations were of natural origin, from springs at the lagoon head with high 228Ra and 226Ra concentrations. The primary source of the Ra in the water was found to be monazite. The radium concentration in surface waters in other parts of the world ranges from 0.01 to 0.1 Bq L1 (Dissanayake and Chandrajith, 2009; Iyengar, 1990). Thus, its (228Ra) concentration in the Buena Lagoon region is twenty-fold higher than the maximum global value. Cullen (1966) has used thermoluminescent dosimeters distributed to 8 age groups throughout the city of Guarapari to measure human exposure to radiation in the city. The results of this 3-month study indicated an average (range of) air equivalent dose rate of 750 (160e2500) mR y1. This result has been confirmed by a later study (Pfeiffer et al., 1981). The reported radioactivity in sand, soil and rock samples collected in four different HBNRAs of BrazileRio de ^nia and the Bikini Janeiro, Guarapari, Poços de Caldas, Goia Atolldindicates that the radiation dose ranges from 3.5 to 10 mSv y1 (Anjos et al., 2004). Pfeiffer et al. (1981) have measured the environmental

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radioactivity in three different areas of distinct geology in Brazil; these areas are located in Guarapari and Meaípe, which are located on the monazite sand belt, in the environs of the uranium mine of Poços de Caldas, and near the site of the first Brazilian nuclear power plant in Angra dos Reis. Among the Brazilian HBNRAs, Poços de Caldas has the highest effective dose: the average annual value has been estimated to be 13 mSv, with a range of 6e16 mSv y1 (Veiga et al., 2003). , and GuarEpidemiological studies of Poços de Caldas, Araxa apari have been conducted based on ten years of mortality data (1991e2000) related to cancer and all other causes (Veiga and Koifman, 2005). This study indicated that the expected cancer mortality was higher than that in the control area in Poços de . It is important to note Caldas and Guarapari and lower in Araxa that this study was based on preliminary investigations; not all deaths that can be linked to cancer are associated with radiation exposure. The lower radiation level and higher cancer incidence in Guarapari indicate that other factors, such as socioeconomic factors, diet, and smoking, exposure to pesticides and other factors related to agricultural activities, may have influenced the results obtained for the area. Although it is a HBNRA, the cancer mortality  is lower than expected, which could be associated with in Araxa deficiencies in the data that have led to problems of confounding and have thus biased the results. Santos et al. (1993) have assessed the activity concentrations of 210 Pb in soil and vegetable samples from the vicinity of the uranium processing mill of Poços de Caldas. The concentrations of 210Pb in the studied soils were found to range from 8 to 220 Bq kg1, which is in agreement with the results of earlier studies conducted by Bunzl and Kracke (1984) and YuD (1974). The geometric means of the radon levels in the air for Poços de Caldas have been reported to be 200 Bq m3 and 61 Bq m3 for rural and urban areas, respectively, and it has been estimated that 16% of all deaths caused by lung cancer in Poços de Caldas may be attributable to radon exposure (Veiga et al., 2003). Gamma radiation has been measured in samples of beach sand collected from Guarapari (and other HBNRAs in Brazil) (Veiga et al., 2006). The average radium equivalent activity in the beach sand collected in Guarapari was found to be ~84 kBq kg1, which is over 200 times higher than the value recommended by the OECD (Organization for Economic Co-operation and Development) for building materials (370 Bq kg1) (OECD, 1997). The highest annual dose rate, 70 mSv, was measured at the Areia Preta beach (Guarapari). Quite low doses (less than unity) have been reported for the sand beaches of Ilha Grande in Rio de Janeiro (Freitas and Alencar, 2004). The average annual dose in Guarapari is 5.5 mSv. Barcinski et al. (1975) have conducted a cytogenetic survey of the inhabitants of Guarapari to investigate the possible biological effects of chronic exposure to natural radiation. A total of 202 and 147 HBNRA and NBRA residents, respectively, were considered by the authors. The total numbers of observed chromosomal breaks were 0.85 ± 1.20 and 0.57 ± 0.93 for the HBNRA and the NBRA, respectively. The authors argued that the observed increase in the total number of chromosome aberrations in the Guarapari residents and its dependence on the individuals and their places of residence could be interpreted as an effect of exposure to elevated radiation caused by the presence of monazite in the coastal beach sands. 2.4. Ramsar (Iran) The elevated level of natural radioactivity in the HBNRAs of Ramsar is caused by 226Ra and its decay products, which have been brought up to the earth's surface by the water of hot springs. There are nine hot springs with varying concentrations of radium in

55

Ramsar, which are used as spas (Ghiassi-nejad et al., 2002; Sohrabi, 1993, 1994). According to the results of surveys performed at the HBNRs of Ramsar, the radioactivity seems to predominantly originate from the mineral water and secondarily from some travertine deposits with higher thorium content than uranium content (Sohrabi, 1993). Sohrabi and Esmaili (2002) have provided extensive data from external radiation studies conducted in both indoors and outdoors, which include the potential annual effective doses to the public in Ramsar. A total of 200 and 800 HBNRAs and NBRAs, respectively were considered by the study. The potential annual effective dose of the public in the HBNRAs was found to range from 0.6 to 131 mSv with a mean value of 6 mSv, and in NBRAs, the observed range was from 0.6 to 1.5 mSv with a mean value of 0.7 mSv. Fig. 1 depicts the source of the high background radioactivity in Ramsar. Igneous bedrocks contain high concentrations of uranium. Although uranium is not soluble in anoxic ground water, its daughter nuclide 226Ra is soluble in ground water. Dissolved radium is transported to the surface by ground water, passing through pores and fractures in the rock. The underground water reaches the surface at hot spring sites. At these sites, calcium carbonate precipitates out of solution and 226Ra substitutes for the calcium (RaCo3). High concentrations of radium carbonate (white in color) are found in the residues of hot springs. In some cases, the residents of these hot spring areas have used the Ra-enriched rock from the hot springs as building materials to construct their houses (Mortazavi et al., 2001; Dissanayake and Chandrajith, 2009). The use of Ra-enriched rocks as building materials has resulted in high indoor concentrations of radon gas. The indoor radon level in Ramsar is as high as 31 kBq m3; the total external and internal exposure leads to an HE value that ranges from 3.0 to 202 mSv y1 and a corresponding 50-year HE of 10.10 Sv for the population. This value is approximately ten-fold the total 50-year dose limit of 1.00 Sv defined for radiation workers (Sohrabi, 2013a; Sohrabi and Babapouran, 2005). The radon exhalation rate in building materials from Ramsar and the primordial radionuclide contents have been reported (Bavarnegin et al., 2013). Studies have reported that some areas in Ramsar have the highest levels of natural radiation in the world with extraordinary radon level (Sohrabi, 2013a; Sohrabi and Babapouran, 2005). Data from these studies show that residents of Talesh Mahalleh in Ramsar receive annual doses as high as 132 mSv from external terrestrial sources and in general, residents of Ramsar receive annual absorbed dose of about 260 mSv y1 from background radiation, which is 20 and 200 times the permitted limit for radiation and non-radiation workers, respectively. The annual effective dose from internal exposure to 222Rn in the HBNRAs of Ramsar ranges from 2.4 to 71.74 mSv (Sohrabi and Babapouran, 2005). Table 3 presents a summary of the biological and epidemiological studies conducted in Ramsar. An increased frequency of chromosome aberration was detected in some studies (Sohrabi, 1998; Zakeri et al., 2011). Other studies (Ghiassi-nejad et al., 2002; Masoomi et al., 2006) have linked the lack of differences between chromosomal aberrations in HBNRAs and NBRAs to adaptive response mechanism. In an earlier cytogenetic study by Fazeli et al. (1993), some chromosomal aberration studies in 10,152 cells of 54 subjects in Talesh Mahalleh of Ramak, 1729 cells of 15 subjects in Talesh Mahalleh of Katalom, and 5969 cells of 34 subjects in the control region showed, respectively, 2.81 ± 0.16, 2.20 ± 0.33 and 1.37 ± 0.18 per 100 cells scored. The results showed a significant positive response in the cytogenetic results of the study group compared to the control group, in particular in the house with the highest level of exposure. A recent study (Taeb et al., 2014) investigated alterations in eight

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Fig. 1. Origin of high natural radioactivity in Ramsar, Iran (Mortazavi et al., 2001).

tumor biomarkers in blood samples from residents of Ramsar. The study found statistically significant correlations between chronic exposure and the concentrations of three of the eight investigated tumor markers. The authors note that the study will contribute to identifying methods of overcoming the limitations of epidemiological studies and will assist Iranian authorities in approving measures intended to decrease the irradiation of Ramsar residents, as suggested by Sohrabi (2013a). On the other hand, cytogenetic studies conducted by Ghiassinejad et al. (2002, 2004) have revealed both adaptive response and increase in chromosomal aberration in Ramsar residents, respectively. In the earlier study, an in vitro challenge dose of 1.5 Gy of gamma rays was administered to the lymphocytes of residents of HBNRAs and NBRAs. The results revealed a significantly reduced frequency of chromosome aberrations in HBNRA residents compared with the residents of the NBRAs. This finding suggested that the HBNRAs residents had developed a resistance to high radiation doses-a phenomenon known as adaptive response. In the later study, the authors considered several immunological and cytogenetic parameters to study the effects of chronic exposure to high background radiation in Ramsar residents. Their results revealed a significant increase in serum IgE and a higher incidence

of chromosomal aberrations in the HBNRA residents. Mosavi-Jarrahi et al. (2005) have investigated the correlation between exposure to elevated background natural radiation and the incidence of cancer mortality. The authors reported a higher mortality rate in female HBNRA residents than in NBRA residents, and this was attributed to the higher indoor radon dose, as most female residents remain indoors. This study found no significant difference in cancer mortality among male residents. The study linked the increase in the incidence of cancer mortality in the HBNRAs of Ramsar to the lifestyle of the female residents. However, a more statistically robust study is required to confirm this conclusion. In another study, Mortazavi et al. (2005) have found a negative correlation between lung cancer rate and radon concentration in the HBNRAs of Ramsar. A review of literature and reports from local physicians show no increase in the incidence rate of cancer or leukemia (Mortazavi et al., 2005; Ghiassi-Nejad et al., 2005). In addition, some studies have shown decrease in cancer mortality with elevated background natural radiation. This finding had lead some researchers to conclude that continued exposure to elevated natural radiation may trigger the production of antioxidants and repair enzymes, and this has been seen in HBNRAs studies in which decreased

Table 3 Effects of chronic exposure to radiation of residents in Ramsar, Iran. HBNRA Country

Ramsar, Iran

Chromosomal aberrations

Cancer data: type (ref.)

Reference

Findings

Reference

Findings

(Sohrabi, 1998)

[

Cancer mortality (Mosavi-Jarrahi et al., 2005)

(Ghiassi-nejad et al., 2004) (Ghiassi-nejad et al., 2004) (Mortazavi and Mozdarani, 2013) (Mortazavi et al., 2006) (Zakeri et al., 2011) (Masoomi et al., 2006)a (Taeb et al., 2014)b

(Adaptive response) 4 [ 4 4 [ (Adaptive response) 4 [

Lung cancer: (Mortazavi et al., 2005)

Female: [ Male: 4 Y

Notes: The symbols [ or Y refer to whether the cited study reported a significant increase or decrease, respectively, in the average frequency of chromosome aberrations per cell or in the incidence of cancer with respect to that in the controls from areas with a normal radiation background. The symbol 4 denotes a lack of any significant difference. a Evaluation of DNA damage. b Evaluation of alteration of tumor biomarkers in human blood serum.

A.S. Aliyu, A.T. Ramli / Radiation Measurements 73 (2015) 51e59

chromosomal aberration were observed. The observed decrease in chromosomal breaks has been linked with the negative correlation between chronic exposure in HBNRAs and increase in cancer incidence. Sohrabi (1998, 2013a) has recommended that remedial actions should be taken to protect the residents of the HBNRAs in Ramsar. The author recommends several specific remedial actions for Ramsar residents, including the adoption of conventional exposure-reduction methodologies, which may entail the renovation and reconstruction of houses and schools. The second remedial action suggested by Sohrabi involves the relocation of the residents and the conversion of the HBNRAs into national environmental radioactivity parks, to be provisionally called “Ramsar Research Natural Radioactivity Parks” (RRNRPs). However, Abdollahi (2013) has argued that there are no significant statistical parameters available to guide decision-making. In Abdollahi's opinion, risk assessment and estimation of detrimental effects requires coping with many methodological limitations and the complexity of the process of radiation carcinogenesis. Hendry et al. (2009) argued that major drawback of the ecological study in Ramsar is the population size of the residents, which is much smaller than those in Kerala and Yangjiang; hence, the number of case studies will necessarily be small, which may lead to some difficulties in collecting observations that reach statistical significance. 3. Discussion A number of epidemiological studies have been conducted to analyze the risk of cancer incidence in the world's HBNRAs. Most of these studies have concluded that there is no link between exposure to high background natural radiation and an increased rate of cancer or mortality. However, the results of these studies should be considered with caution because of the confounding factors associated with their methodology. For instance, Wei et al. (1990) have observed an increase in the incidence of Down's syndrome among Chinese HBNRA residents. However, the findings of this study have also been linked to other factors, such as the difference in the age of maternity between the HBNRA and NBRA residents. To address this difficulty associated with epidemiological studies of HBNRAs, coordinated research programs should be launched as a collaborated effort among countries with HBNRAs, supported by relevant international bodies (e.g., IAEA and WHO), to develop strong research designs based on robust statistics and sufficient data. This will, in turn, create lines of communication for standardized data collection and dissemination among scientists working in this field. Chromosomal aberration is undoubtedly a reliable biodosimetric tool; however, several HBNRA studies have indicated correlations between an increase in the frequency of chromosomal aberration with no accompanying evidence of any excess risk of cancer in these HBNRAs. The failure of past epidemiological studies to indicate any significant increase in cancer rate in HBNRAs has been used to call into question the validity of the LNT extrapolation of doseeresponse relationships in the low-dose and low-dose-rate regime (Karam, 2002; Mortazavi and Mozdarani, 2013; Abdollahi, 2013). The absence of an excess of cancers in HBNRAs has been interpreted as supporting evidence for the beneficial effects of exposure to radiation. Unfortunately, it is probably too early to draw any definitive conclusion either way on this topic because most (with a few exceptions) studies of the rate of cancer incidence and dose response in HBNRAs have not been conducted with sufficient sample sizes, replication, or controls and hence may not be truly representative of reality. Mortazavi et al. (2005) have reported a negative correlation

57

between the incidence of lung cancer and the extraordinary level of radon gas in the homes of Ramsar residents. By contrast, there is more reliable evidence that indoor radon studies indicate an elevation of lung cancer risk even for levels of exposure as low as 200 Bq m3 (Darby et al., 2005). The lack of availability of reliable and up-to-date records in HBNRAs has led to irrational conclusions in some epidemiological studies. In Spain, for instance, efforts have been made to measure the radon levels in houses, and most importantly, the indoor radon concentration in Spain's HBNRA (Villar de la Yegua) has been reported to be approximately 15 kBq m3, with an HE as high as  s Poncela et al., 2004). A geometric mean 267 mSv y1 (Quindo radon concentration of ~13.6 kBq m3 has been reported for Villar de la Yegua, as well as a lifetime risk of lung cancer of almost 30%, which is 35 times higher than that of the general Spanish population (Sainz et al., 2007). In a more recent study, Sainz et al. (2010) constructed an experimental pilot house in the Villar de la Yegua village with the objective of radon mitigation. Some of the remedial actions tested in the experimental pilot house included central natural ventilation, lateral natural ventilation, central forced extraction, central pressurization, crossed ventilation and radon barriers. The use of radon barriers was found to be the most effective mitigation methodology. Through cooperation with other European countries, Spain has kept up-to-date records of radon measurements, and regulations have been instituted in an effort toward mitigation (Darby et al., 2005); recently, an updated version of the Spanish indoor radon map has been produced (SainzFernandez et al., 2014). More efforts should be directed toward radon measurement and mitigation in world's HBNRAs with extraordinary radon level (e.g. Ramsar), and adopting and improving on the Spanish model may provide a good starting point. 4. Conclusion This paper presented an overview of studies of the HBNRAs. The radiological, epidemiological and radiobiological issues related to these HBNRAs were highlighted, with the intent of stimulating further research and discussion. Coordinated efforts have been in place to address some of the problems that are associated with HBNRAs epidemiology; for example the chain of HBNRA conferences, cooperation between Japan, China, India, Iran, and the IAEA coordinated effort through a project which lead to the review by Hendry et al. (2009), have contributed to a deeper understanding of the radiation risk in HBNRAs. In order to address the problems encountered by epidemiological studies of HBNRAs, more coordinated research programs should be launched as collaborative efforts among countries with HBNRAs, supported by relevant international bodies (e.g., IAEA and WHO). This will lead to the development of strong research designs that are based on robust statistics and sufficient data. This will also fulfill the gaps existing in the data of each HBNRA. The international collaboration will create lines of communication for standardized data collection and dissemination among scientists working in the field. The difficulties in conducting strong epidemiologic investigations of the HBNRAs, can be addressed by conducting carefully designed epidemiological studies by international experts in the field of epidemiology. Acknowledgments A.S. Aliyu wishes to acknowledge the support of the Research Management Center of Universiti Teknologi Malaysia for its support through the Post-Doctoral fellowship scheme under the project number (Q.J130000.21A2.01E98).

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