Thyroid doses due to Iodine-131 inhalation among Chernobyl cleanup workers.

Several hundred thousand individuals, called 'cleanup workers' or 'liquidators', who took part in decontamination and recovery activities between 1986 and 1990 within the 30-km zone around the Chernobyl nuclear power plant in Ukraine, were mainly exposed to external irradiation. However, those who were involved in cleanup activities during the 10-day period of atmospheric releases also received doses to the thyroid gland due to internal irradiation resulting essentially from inhalation of 131I. The paper presents the methodology and results of the calculation of individual thyroid doses for cleanup workers. The model that was used considers several factors, including the ground-level outdoor air concentrations of 131I at the locations of residence and work of the cleanup workers, the reduction of 131I activity in inhaled air associated with indoor occupancy, the time spent indoors, the breathing rate, which depends on the type of physical activity, and the possible intake of potassium iodine (KI) for iodine prophylaxis. Thyroid doses were calculated for a group of 594 cleanup workers with individual measurements of exposure rate against the neck, called 'direct thyroid measurements', that were performed from 30 April to 5 May 1986. The measured values of exposure rate were corrected to subtract the contribution of short-lived radioiodine isotopes in the thyroid to the detector response. The average thyroid dose due to 131I inhalation by the cleanup workers was estimated to be 180 mGy, while the median was 110 mGy. Most of the cleanup workers (73%) received thyroid doses ranging from 50 to 500 mGy. The highest individual dose from 131I inhalation among the cleanup workers with direct thyroid measurements was 4.5 Gy. To validate the model, the 131I activities in the thyroids that were calculated using the model were compared with those derived from the direct thyroid measurements. The mean of the ratios of measured-to-calculated activities of 131I in the thyroid was found to be 1.6 while the median of those ratios was 0.8. For 60 cleanup workers with direct thyroid measurements, a detailed description of hour-by-hour whereabouts and work history was available. For these cleanup workers the mean of the ratios of measured-to-calculated activities was found to be 1.2 and the median of those ratios was 1.0. These encouraging results suggest that the thyroid dose due to 131I inhalation could be estimated for Chernobyl cleanup workers with a reasonable degree of reliability even in the absence of direct thyroid measurements. However, this conclusion assumes that detailed information on whereabouts and work history could be obtained for those cleanup workers who were not measured.

Influence of the external and internal radioactive contamination of the body and the clothes on the results of the thyroidal 131I measurements conducted in Belarus after the Chernobyl accident-Part 2: Monte Carlo simulation of response of detectors near the thyroid.

This paper describes the calculation of the response of the most common types of radiation detectors that were used within the first few weeks after the Chernobyl accident to determine the activity of 131I in the thyroids of Belarusian subjects of an epidemiologic study of thyroid cancer. The radiation detectors, which were placed against the necks of the subjects, measured the exposure rates due to the emission of gamma rays resulting from the radioactive decay of 131I in their thyroids. Because of the external and internal radioactive contamination of the monitored subjects, gamma radiation from many radionuclides in various locations contributed to the exposure rates recorded by the detectors. To estimate accurately the contribution from gamma rays emitted from various internal and external parts of the body, the calibration factors of the radiation detectors, expressed in kBq per µR h- 1, were calculated, by means of Monte Carlo simulation, for external irradiation from unit activities of 17 radionuclides located on 19 parts of the body, as well as for internal irradiation from the same 17 radionuclides in the lungs, from caesium radionuclides distributed uniformly in the whole body, and from 131I in the thyroid. The calculations were performed for six body sizes, representative of the age range of the subjects. In a companion paper, the levels of external and internal contamination of the body were estimated for a variety of exposure conditions. The results presented in the two papers were combined to calculate the 131I activities in the thyroids of all 11,732 Belarusian study subjects of an epidemiologic study of thyroid cancer and, in turn, their thyroid doses.

Influence of the external and internal radioactive contamination of the body and the clothes on the results of the thyroidal 131I measurements conducted in Belarus after the Chernobyl accident. Part 1: Estimation of the external and internal radioactive contamination.

The estimation of the thyroid doses received in Belarus after the Chernobyl accident is based on the analysis of exposure-rate measurements performed with radiation detectors placed against the necks of about 130,000 residents. The purpose of these measurements was to estimate the 131I activity contents of the thyroids of the subjects. However, because the radiation detectors were not equipped with collimators and because the subjects usually wore contaminated clothes, among other factors, the radiation signal included, in addition to the gamma rays emitted during the decay of the 131I activity present in the thyroid, contributions from external contamination of the skin and clothes and internal contamination of organs other than the thyroid by various radionuclides. The assessment of the contributions of the external and internal contamination of the body to the radiation signal is divided into two parts: (1) the estimation of the radionuclide activities deposited on, and incorporated in, various parts of the body, and (2) the responses of the radiation detectors to the gamma rays emitted by the radionuclides deposited on, and incorporated in, various parts of the body. The first part, which is presented in this paper, includes a variety of exposure scenarios, models, and calculations for 17 of the most abundant gamma-emitting radionuclides contributing to the thyroid detector signal, while the second part is presented in a companion paper. The results presented in the two papers were combined to calculate the contributions of the external and internal contamination of the body to the radiation signal, and, in turn, the 131I activities in the thyroids of all subjects of an epidemiologic study of thyroid cancer and other thyroid diseases among 11,732 Belarusian-American cohort members who were exposed in childhood and adolescence.

Clinical characteristics of chronic lymphocytic leukemia occurring in chornobyl cleanup workers.

The recently demonstrated radiation-induction of chronic lymphocytic leukemia (CLL) raises the question as to whether the amount of radiation exposure influences any of the clinical characteristics of the disease. We evaluated the relationship between bone marrow radiation doses and clinical characteristics and survival of 79 CLL cases diagnosed during 1986-2006 in a cohort of 110 645 male workers who participated in the cleanup work of the Chornobyl nuclear accident in Ukraine in 1986. All diagnoses were confirmed by an independent International Hematology Panel. Patients were followed up to the date of death or end of follow-up on 31 October 2010. The median age at diagnosis was 57 years. Median bone marrow dose was 22.6 milligray (mGy) and was not associated with time between exposure and clinical diagnosis of CLL (latent period), age, peripheral blood lymphocyte count or clinical stage of disease in univariate and multivariate analyses. Latent period was significantly shorter among those older at first exposure, smokers and those with higher frequency of visits to the doctor prior to diagnosis. A significant increase in the risk of death with increasing radiation dose was observed (p = 0.03, hazard ratio = 2.38, 95% confidence interval: 1.11,5.08 comparing those with doses ≥22 mGy to doses <22 mGy). After adjustment for radiation dose, survival of CLL cases was significantly shorter among those with younger age at first exposure, higher peripheral blood lymphocyte count, more advanced clinical stage of disease and older age at diagnosis (all p < 0.05). This is the first study to examine association between bone marrow radiation doses from the Chornobyl accident and clinical manifestations of the CLL in Chornobyl cleanup workers. The current study provides new evidence on the association of radiation dose and younger age at first radiation exposure at Chornobyl with shorter survival after diagnosis. Future studies are necessary with more cases in order to improve the statistical power of these analyses and to determine their significance. Copyright © 2016 John Wiley & Sons, Ltd.

Neonatal outcomes following exposure in utero to fallout from Chernobyl.

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (-1.0 cm/Gy, P = 0.005) and chest circumference (-0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (-0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

Doses for post-Chernobyl epidemiological studies: are they reliable?

On 26 April 2016, thirty years will have elapsed since the occurrence of the Chernobyl accident, which has so far been the most severe in the history of the nuclear reactor industry. Numerous epidemiological studies were conducted to evaluate the possible health consequences of the accident. Since the credibility of the association between the radiation exposure and health outcome is highly dependent on the adequacy of the dosimetric quantities used in these studies, this paper makes an effort to overview the methods used to estimate individual doses and the associated uncertainties in the main analytical epidemiological studies (i.e. cohort or case-control) related to the Chernobyl accident. Based on the thorough analysis and comparison with other radiation studies, the authors conclude that individual doses for the Chernobyl analytical epidemiological studies have been calculated with a relatively high degree of reliability and well-characterized uncertainties, and that they compare favorably with many other non-Chernobyl studies. The major strengths of the Chernobyl studies are: (1) they are grounded on a large number of measurements, either performed on humans or made in the environment; and (2) extensive effort has been invested to evaluate the uncertainties associated with the dose estimates. Nevertheless, gaps in the methodology are identified and suggestions for the possible improvement of the current dose estimates are made.

Risk of thyroid follicular adenoma among children and adolescents in Belarus exposed to iodine-131 after the Chornobyl accident.

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at <2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the (131)I-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure.

Analysis of thyroid malignant pathologic findings identified during 3 rounds of screening (1997-2008) of a cohort of children and adolescents from belarus exposed to radioiodines after the Chernobyl accident.

BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS: A cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (P < .01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P < .03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P < .0001). CONCLUSIONS: I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness.

Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci.

Background: Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations. Methods: We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population. Results: We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10-7, 2.39 × 10-7, and 7.19 × 10-7 and corresponding odds ratios of 2.02, 1.89, and 2.37. Conclusion: Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.

Assessment of Differentiated Thyroid Carcinomas in French Polynesia After Atmospheric Nuclear Tests Performed by France.

Importance: Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains a controversial issue in medicine and public health, and a misunderstanding of this issue may be associated with overdiagnosis of DTCs. Design, Setting, and Participants: This case-control study was conducted by extending a case-control study published in 2010 that included DTCs diagnosed between 1984 and 2003 by adding DTCs diagnosed between 2004 and 2016 and improving the dose assessment methodology. Data on 41 atmospheric nuclear tests conducted by France between 1966 and 1974 in French Polynesia (FP) were assessed from original internal radiation-protection reports, which the French military declassified in 2013 and which included measurements in soil, air, water, milk, and food in all FP archipelagos. These original reports led to an upward reassessment of the nuclear fallout from the tests and a doubling of estimates of the mean thyroid radiation dose received by inhabitants from 2 mGy to nearly 5 mGy. Included patients were diagnosed from 1984 to 2016 with DTC at age 55 years or younger and were born in and resided in FP at diagnosis; 395 of 457 eligible cases were included, and up to 2 controls per case nearest by birthdate and matched on sex were identified from the FP birth registry. Data were analyzed from March 2019 through October 2021. Exposure: The radiation dose to the thyroid gland was estimated using recently declassified original radiation-protection service reports, meteorological reports, self-reported lifestyle information, and group interviews of key informants and female individuals who had children at the time of these tests. Main Outcomes and Measures: The lifetime risk of DTC based on Biological Effects of Ionizing Radiation (BEIR) VII models was estimated. Results: A total of 395 DTC cases (336 females [85.1%]; mean [SD] age at end of follow-up, 43.6 [12.9] years) and 555 controls (473 females [85.2%]; mean [SD] age at end of follow-up, 42.3 [12.5] years) were included. No association was found between thyroid radiation dose received before age 15 years and risk of DTC (excess relative risk [ERR] per milligray, 0.04; 95% CI, -0.09 to 0.17; P = .27). When excluding unifocal noninvasive microcarcinomas, the dose response was significant (ERR per milligray, 0.09; 95% CI, -0.03 to 0.02; P = .02), but several incoherencies with the results of the initial study reduce the credibility of this result. The lifetime risk for the entire FP population was 29 cases of DTC (95% CI, 8-97 cases), or 2.3% (95% CI, 0.6%-7.7%) of 1524 sporadic DTC cases in this population. Conclusions and Relevance: This case-control study found that French nuclear tests were associated with an increase in lifetime risk of PTC in FP residents of 29 cases of PTC. This finding suggests that the number of thyroid cancer cases and the true order of magnitude of health outcomes associated with these nuclear tests were small, which may reassure populations of this Pacific territory.

Thyroid cancer in Ukraine after the Chernobyl accident (in the framework of the Ukraine-US Thyroid Project).

As a result of the accident at the Chernobyl Nuclear Power Plant, millions of residents of Belarus, Russia, and Ukraine were exposed to large doses of radioactive iodine isotopes, mainly I-131. The purpose of the Ukraine-American (UkrAm) and Belarus-American (BelAm) projects are to quantify the risks of thyroid cancer in the framework of a classical cohort study, comprising subjects who were aged under 18 years at the time of the accident, had direct measurements of thyroid I-131 radioactivity taken within two months after the accident, and were residents of three heavily contaminated northern regions of Ukraine (Zhitomir, Kiev, and Chernigov regions). Four two-year screening examination cycles were implemented from 1998 until 2007 to study the risks associated with thyroid cancer due to the iodine exposure caused during the Chernobyl accident. A standardised procedure of clinical examinations included: thyroid palpation, ultrasound examination, blood collection followed by a determination of thyroid hormone levels, urinary iodine content test, and fine-needle aspiration if required. Among the 110 cases of thyroid cancer diagnosed in UkrAm as the result of four screening examinations, 104 cases (94.5%) of papillary carcinomas, five cases (4.6%) of follicular carcinomas, and one case (0.9%) of medullary carcinoma were diagnosed.

Evaluation of 131I transfer in the environment based on the available measurements made in Belarus after the Chernobyl accident.

This study evaluates the 131I transfer from ground deposition to the human thyroid gland after the Chernobyl accident using measurements of 131I concentrations in 1,252 soil, 124 grass, and 136 cow's milk samples as well as 131I thyroid activity measured in 3,100 individuals included in the Belarusian-American cohort. The following parameters of an 131I environmental transfer model used to calculate thyroid doses were evaluated in this study: (i) the interception factor of 131I by pasture grass, which was described by a purely empirical equation, (ii) the removal rate of 131I from pasture grass due to weathering and growth dilution, estimated to be 0.0676 d-1 (half-life of 10.3 d), (iii) the removal rate of 131I from cow's milk, estimated to be 0.0686 d-1 (half-life of 10.1 d), and (iv) the transfer coefficient of 131I from feed to cow's milk, arithmetic mean ± standard deviation of (6.7 ± 8.7) × 10-3 d L-1 (median = 4.0 × 10-3 d L-1). The individual model-based and measurement-based 131I thyroid activities for the Belarusian-American cohort members were calculated using different starting points of 131I transfer in the chain 'ground deposition' → 'vegetation' → 'cow's milk' → 'human thyroid', i.e., the measured 131I concentrations in soil, grass, and cow's milk. De novo thyroid doses from 131I for the 3,100 cohort members were calculated in this study using measured 131I activity concentrations in soil, grass, and cow's milk and were compared with those estimated previously for the same individuals using model-based 131I activity concentrations. It was shown that the use of measured instead of model-based 131I concentrations, in general, did not improve the measurement-based thyroid dose estimates. This is likely to be because there was already a good generic data base for the parameters used in this assessment. This finding indicates that, although the measurements of environmental samples are essential to estimate the parameter values of the 131I transfer model, the individual measurements of 131I thyroid activity are the most valuable information for estimating individual thyroid doses.

Dose Coefficients for Internal Dose Assessments for Exposure to Radioactive Fallout.

ABSTRACT: This paper presents values as well as the bases for calculating internal dose coefficients suitable for estimating organ doses from the exposure to radioactive fallout that could result from the detonation of a nuclear fission device. The 34 radionuclides discussed are the same as those given in a priority list of radionuclides for fallout dose assessments presented in a companion overview paper. The radionuclides discussed are those that are believed to account for a preponderance of the organ doses that might be received by intake by persons of all ages (including in utero and via breast feeding for infants) following exposure to radioactive fallout. The presented dose coefficients for ingestion account for age and include modifications for variations in solubility with distance as discussed previously in the literature, and those for inhalation similarly account for age, solubility, and particle sizes that would be relevant at various distances of exposure as discussed in a companion paper on ingestion dose methods. The proposed modifications peculiar to radioactive fallout account for systematic changes in solubility and particle sizes with distance from the site of detonation, termed here as the region of "local fallout" and the region "beyond local fallout." Brief definitions of these regions are provided here with more detailed discussion in a companion paper on estimating deposition of fallout radionuclides. This paper provides the dose coefficients for ingestion and inhalation (for particle sizes of 1 µm, 5 µm, 10 µm, and 20 µm) for the region "local fallout." These dose coefficients for "local fallout" are specific for particles formed in a nuclear explosion that can be large and have radionuclides, particularly the more refractory ones, distributed throughout the volume where the radionuclide has reduced solubility. The dose coefficients for the region "beyond local fallout" are assumed to be the ones published by the International Commission on Radiological Protection (ICRP) in 1995. Comparisons of the presented dose coefficients are made with values published by the ICRP.

Dose Estimation for Exposure to Radioactive Fallout from Nuclear Detonations.

ABSTRACT: In recent years, the prospects that a nuclear device might be detonated due to a regional or global political conflict, by violation of present nuclear weapons test ban agreements, or due to an act of terrorism, has increased. Thus, the need exists for a well conceptualized, well described, and internally consistent methodology for dose estimation that takes full advantage of the experience gained over the last 70 y in both measurement technology and dose assessment methodology. Here, the models, rationale, and data needed for a detailed state-of-the-art dose assessment for exposure to radioactive fallout from nuclear detonations discussed in five companion papers are summarized. These five papers present methods and data for estimating radionuclide deposition of fallout radionuclides, internal and external dose from the deposited fallout, and discussion of the uncertainties in the assessed doses. In addition, this paper includes a brief discussion of secondary issues related to assessments of radiation dose from fallout. The intention of this work is to provide a usable and consistent methodology for both prospective and retrospective assessments of exposure from radioactive fallout from a nuclear detonation.

A Method for Estimating the Deposition Density of Fallout on the Ground and on Vegetation from a Low-yield, Low-altitude Nuclear Detonation.

ABSTRACT: This paper describes a relatively simple model developed from observations of local fallout from US and USSR nuclear tests that allows reasonable estimates to be made of the deposition density (activity per unit area) on both the ground and on vegetation for each radionuclide of interest produced in a nuclear fission detonation as a function of location and time after the explosion. In addition to accounting for decay rate and in-growth of radionuclides, the model accounts for the fractionation (modification of the relative activity of various fission and activation products in fallout relative to that produced in the explosion) that results from differences in the condensation temperatures of the various fission and activation products produced in the explosion. The proposed methodology can be used to estimate the deposition density of all fallout radionuclides produced in a low yield, low altitude fission detonation that contribute significantly to dose. The method requires only data from post-detonation measurements of exposure rate (or beta or a specific nuclide activity) and fallout time-of-arrival. These deposition-density estimates allow retrospective as well as rapid prospective estimates to be made of both external and internal radiation exposure to downwind populations living within a few hundred kilometers of ground zero, as described in the companion papers in this volume.

A Methodology for Estimating External Doses to Individuals and Populations Exposed to Radioactive Fallout from Nuclear Detonations.

ABSTRACT: A methodology of assessment of the doses from external irradiation resulting from the ground deposition of radioactive debris (fallout) from a nuclear detonation is proposed in this paper. The input data used to apply this methodology for a particular location are the outdoor exposure rate at any time after deposition of fallout and the time-of-arrival of fallout, as indicated and discussed in a companion paper titled "A Method for Estimating the Deposition Density of Fallout on the Ground and on Vegetation from a Low-yield Low-altitude Nuclear Detonation." Example doses are estimated for several age categories and for all radiosensitive organs and tissues identified in the most recent ICRP publications. Doses are calculated for the first year after the detonation, when more than 90% of the external dose is delivered for populations close to the detonation site over a time period of 70 y, which is intended to represent the lifetime dose. Modeled doses in their simplest form assume no environmental remediation, though modifications can be introduced. Two types of dose assessment are considered: (1) initial, for a rapid but only approximate dose estimation soon after the nuclear detonation; and (2) improved, for a later, more accurate, dose assessment following the analysis of post-detonation measurements of radiation exposure and fallout deposition and the access of information on the lifestyle of the exposed population.