Päivi Kurttio

Bone as a possible target of chemical toxicity of natural uranium in drinking water.

Uranium accumulates in bone, affects bone metabolism in laboratory animals, and when ingested in drinking water increases urinary excretion of calcium and phosphate, important components in the bone structure. However, little is known about bone effects of ingested natural uranium in humans. We studied 146 men and 142 women 26–83 years of age who for an average of 13 years had used drinking water originating from wells drilled in bedrock, in areas with naturally high uranium content. Biochemical indicators of bone formation were serum osteocalcin and amino-terminal propeptide of type I procollagen, and a marker for bone resorption was serum type I collagen carboxy-terminal telopeptide (CTx). The primary measure of uranium exposure was uranium concentration in drinking water, with additional information on uranium intake and uranium concentration in urine. The data were analyzed separately for men and women with robust regression (which suppresses contributions of potential influential observations) models with adjustment for age, smoking, and estrogen use. The median uranium concentration in drinking water was 27 μg/L (interquartile range, 6–116 μg/L). The median of daily uranium intake was 36 μg (7–207 μg) and of cumulative intake 0.12 g (0.02–0.66 g). There was some suggestion that elevation of CTx (p = 0.05) as well as osteocalcin (p = 0.19) could be associated with increased uranium exposure (uranium in water and intakes) in men, but no similar relationship was found in women. Accordingly, bone may be a target of chemical toxicity of uranium in humans, and more detailed evaluation of bone effects of natural uranium is warranted.

Validation of short term recall of mobile phone use for the Interphone study

Aim: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. Methods: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. Results: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. Conclusions: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Acoustic neuroma risk in relation to mobile telephone use: Results of the INTERPHONE international case-control study

BACKGROUND The rapid increase in mobile telephone use has generated concern about possible health risks of radiofrequency electromagnetic fields from these devices. METHODS A case-control study of 1105 patients with newly diagnosed acoustic neuroma (vestibular schwannoma) and 2145 controls was conducted in 13 countries using a common protocol. Past mobile phone use was assessed by personal interview. In the primary analysis, exposure time was censored at one year before the reference date (date of diagnosis for cases and date of diagnosis of the matched case for controls); analyses censoring exposure at five years before the reference date were also done to allow for a possible longer latent period. RESULTS The odds ratio (OR) of acoustic neuroma with ever having been a regular mobile phone user was 0.85 (95% confidence interval 0.69-1.04). The OR for ≥10 years after first regular mobile phone use was 0.76 (0.52-1.11). There was no trend of increasing ORs with increasing cumulative call time or cumulative number of calls, with the lowest OR (0.48 (0.30-0.78)) observed in the 9th decile of cumulative call time. In the 10th decile (≥1640 h) of cumulative call time, the OR was 1.32 (0.88-1.97); there were, however, implausible values of reported use in those with ≥1640 h of accumulated mobile phone use. With censoring at 5 years before the reference date the OR for ≥10 years after first regular mobile phone use was 0.83 (0.58-1.19) and for ≥1640 h of cumulative call time it was 2.79 (1.51-5.16), but again with no trend in the lower nine deciles and with the lowest OR in the 9th decile. In general, ORs were not greater in subjects who reported usual phone use on the same side of the head as their tumour than in those who reported it on the opposite side, but it was greater in those in the 10th decile of cumulative hours of use. CONCLUSIONS There was no increase in risk of acoustic neuroma with ever regular use of a mobile phone or for users who began regular use 10 years or more before the reference date. Elevated odds ratios observed at the highest level of cumulative call time could be due to chance, reporting bias or a causal effect. As acoustic neuroma is usually a slowly growing tumour, the interval between introduction of mobile phones and occurrence of the tumour might have been too short to observe an effect, if there is one.

Association Between the Clastogenic Effect in Peripheral Lymphocytes and Human Exposure to Arsenic Through Drinking Water

We describe the association between structural chromosome aberrations (CAs) and parameters of exposure to arsenic among 42 individuals exposed to arsenic through well waters in Finland. The median concentration of arsenic in the wells was 410 μg/l, the total arsenic concentrations in urine (As‐tot) was 180 μg/l, and in hair 1.3 μg/g, for current users (n = 32) of contaminated wells. Urinary arsenic species and CAs were also analyzed in eight control individuals from the same village who consumed water which contained arsenic <1.0 μg/l (detection limit). Increased arsenic exposure, indicated best by increased concentrations of arsenic species (inorganic arsenic, methylarsonic acid (MMA), dimethylarsinic acid (DMA)) in urine, was associated with increased frequency of CAs. The increased urinary ratio of MMA/As‐tot and the decreased ratio of DMA/As‐tot were associated with increased CAs when all aberration types, including gaps, were considered. Associations between CAs and arsenic exposure indicators were stronger among current users than among persons who had stopped using the contaminated well water for 2–4 months before sampling (ex‐users, n = 10). Furthermore, there was a positive but not statistically significant association between CAs and arsenic in hair among the current users, but not among the ex‐users, who still had relatively high arsenic concentrations in hair. The results suggest that the effect observed in the present study reflects relatively recent arsenic exposure. Environ. Mol. Mutagen. 32: 301–313, 1998

Radon and other natural radionuclides in drinking water and risk of stomach cancer: A case-cohort study in Finland

Very high concentrations of naturally occurring radionuclides are encountered in Finnish groundwaters and wells. Radon ingested through drinking water can cause considerable radiation to the stomach. We assessed the effect of natural uranium and other radionuclides in drinking water on the risk of stomach cancer. Subjects (n = 144,627) in the base cohort had lived outside the municipal tap water system during 1967–1980. A subcohort of 4,590 subjects was formed for use as a reference group by random sampling of the base cohort, with stratification by age and sex. Within the subcohort, 371 subjects had used drinking water from drilled wells prior to 1981. Stomach cancer cases within the subcohort were identified through a cancer registry, and cases using water from drilled wells were selected. Activity concentrations of radon, radium‐226 and natural uranium in the drinking water were analyzed using radiochemical and alpha spectrometric methods. The median activity concentration of radon in well water was 130 Bq/l for both the 88 stomach cancer cases and the 274 subjects in the subcohort. Median radium concentrations were 0.007 Bq/l for cases and 0.010 Bq/l for the subcohort, with a median uranium concentration of 0.07 Bq/l for both groups. Risk of stomach cancer was not associated with exposure to radon or other radionuclides. The hazard ratio of stomach cancer was 0.68 for radon (95% CI 0.29–1.59 at 100 Bq/l water), 0.69 per Bq/1 for radium‐226 (95% CI 0.33–1.47) and 0.76 per Bq/1 for uranium (95% CI 0.48–1.21). Our results do not indicate an increased risk of stomach cancer from ingestion of radon or other natural radionuclides through drinking water at these exposure levels.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment

Objectives: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. Methods: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual’s phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. Results: Measurements of over 60 000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. Conclusions: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Lens Opacities among Physicians Occupationally Exposed to Ionizing radiation-a Pilot Study in Finland

OBJECTIVES The aim of this study was to estimate the prevalence of lens opacities among physicians occupationally exposed to radiation - overall and by occupational factors - and to assess the feasibility of a large-scale study for risk assessment. METHODS Based on a nationwide registry of 1312 physicians, mostly radiologists with occupational exposure to ionizing radiation, 120 subjects were invited to participate, of which 59 (49%) consented. The inclusion criteria included (i) age 45-70 years, (ii) cumulative recorded radiation dose >10 mSv, and (iii) duration of work with dose monitoring >15 years. The participants completed a questionnaire regarding occupational history and other risk factors for lens opacities. A full ophthalmological examination was performed. Lenticular changes were graded using the Lens Opacities Classification System, version II (LOCS II), and the Nidek EAS-1000 Scheimpflug slit-imaging videophotography system. RESULTS Lens opacities were detected in 42% [95% confidence interval (95% CI) 29-55] of the 57 physicians without prior cataract surgery. Nuclear opacities were found in 14% (95% CI 6-26), cortical in 7% (95% CI 2-19), and posterior subcapsular in 5% (95% CI 1-15) of the subjects. The prevalence of lens opacities increased with age, smoking, and cumulative recorded radiation dose. After controlling for age, gender, and smoking, the excess odds ratio for any lens opacity was 0.13 (95% CI -0.02-0.28) per 10 mSv of cumulative radiation dose. CONCLUSIONS Our preliminary results show cortical and posterior subcapsular lens opacities among physicians exposed to occupational radiation, consistent with recent studies on low dose radiation exposure. A full study with an unexposed reference group for risk estimation is warranted.

Increased mercury exposure in inhabitants living in the vicinity of a hazardous waste incinerator : A 10-year follow-up

A hazardous-waste-treatment plant that housed an incinerator began operation in 1984, before which a baseline survey of the surrounding population and environment was conducted; 10 y later, investigators studied the same subjects. Researchers focused on mercury exposure because mercury concentrations were present in the stack emissions, and environmental monitoring revealed mercury concentrations near the plant. In 1984 and 1994 the median hair mercury concentrations were 0.5 mg/kg and 0.8 mg/kg, respectively. During the 10-y period, median hair total mercury concentrations increased by 0.35 mg/kg in workers (n = 11); by 0.16 mg/kg, 0.13 mg/kg, and 0.03 mg/kg in individuals who lived 2 km (n = 45), 2-4 km (n = 38), and 5 km (n = 30) from the plant, respectively; and by 0.02 mg/kg in the reference group (n = 55). In summary, mercury exposure increased as distance from the plant decreased; however, the increase in exposure was minimal and, on the basis of current knowledge, did not pose a health risk.

Mobile phone use and location of glioma: a case-case analysis.

We assessed a new approach for evaluating the glioma risk among users of mobile phones to focus on the part of the brain most heavily exposed to radiofrequency electromagnetic fields from mobile phones. The tumor midpoint was defined from radiological imaging. A case-case analysis with 99 gliomas was performed using logistic regression. The exposed cases were those with the tumor mid-point within 4.6 cm from the line between the mouth and the external meatus of the ear, representing the most likely location of the mobile phone (the source of exposure). Alternative analyses based on various indicators of mobile phone use as the outcome were also carried out. The majority of cases were regular mobile phone users. A slightly higher proportion of gliomas among mobile phone users than non-users occurred within 4.6 cm from the presumed location of the mobile phone (28% vs. 14%). Modestly elevated odds ratios were observed for several indicators of mobile phone use, but without an exposure gradient. The highest odds ratios were found for contralateral and short-term use. Our results, though limited by the small sample size, demonstrate that detailed information on tumor location allows evaluation of the risk related to the most heavily exposed part of the brain, representing direct evaluation of the possible local carcinogenic effects of the radiofrequency fields. However, field strength varies between users and over time also within a given anatomic site, due to the output power of the phone. Collaborative analysis of a larger sample is planned.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides-Cutaneous T-cell lymphoma: Clinical implications

Mycosis fungoides (MF) is the most common variant of primary cutaneous T‐cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia‐inducible factor 1 alpha (HIF‐1α) may regulate FoxP3 expression; however, it is unknown whether HIF‐1α is expressed in the CD4+ T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF‐1α and FoxP3 in CD4+ T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4+ T cells with an aberrant phenotype among early stage MF patients. HIF‐1α was overexpressed in these CD4+ T cells. In addition, we found a decrease in the percentage of FoxP3+ cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF‐1α and FoxP3 expression. Skin HIF‐1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF‐1α degradation increases the percentage of FoxP3+ T cells in skin lesions. Our results suggest that overexpression of HIF‐1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.