Development and validation of a modified QuEChERS protocol coupled to UHPLC-APCI-MS/MS for the simple and rapid quantification of 16 heterocyclic aromatic amines in cooked beef.

Heterocyclic aromatic amines (HAAs) are neo-formed compounds generated during the cooking of meats and are known or suspected to be mutagenic and carcinogenic. In this study, a novel, simple, and fast methodology combining salting-out liquid-liquid microextraction, solid-phase extraction (SPE), and UHPLC-APCI-MS/MS was developed for the analysis of 16 HAAs. The QuEChERS extraction (quick, easy, cheap, efficient, rugged, and safe) was revisited and modified using mixed-mode SPE purification to adapt the method to the particular physicochemical properties of HAAs and the fatty nature of the beef matrix. The UHPLC-MS/MS analysis was performed on a C8 column in less than 4 min using positive APCI ionisation and an internal standard. The method was validated according to the European Medicines Agency and Eurachem guidelines and was successfully applied to beef samples of various cooking degrees, showing HAA levels similar to those shown by previous studies.

Inventory and vertical distribution of 137Cs, 239+240Pu and 238Pu in soil from Raivavae and Hiva Oa, two French Polynesian islands in the southern hemisphere.

Atmospheric nuclear weapons tests carried out by the United States, the former Soviet Union, the United Kingdom, France and China between 1945 and 1980 resulted in radioactive fallout over the earth's surface of long-lived radionuclides, such as 137Cs, 239+240Pu and 238Pu that could be detected more than 50 years after their production. In addition, the burnup in the upper atmosphere of a thermoelectric generator fueled by 238Pu, SNAP-9A, contributed to the inventory of 238Pu deposited on the ground. In order to estimate the deposition densities of 137Cs, 239+240Pu and 238Pu in French Polynesia, we collected undisturbed soil samples up to 30 cm deep at eight sites in two islands (Hiva Oa, 139°W - 10°S and Raivavae, 148°W - 24°S) in 2015-2016. The top 0-10 cm of the soil cores were sliced into five 2-cm layers and the bottom 10-30 cm into four 5-cm layers for gamma spectrometry and alpha spectrometry measurements. We found that more than 50% of the radioactive inventories are still contained within the first 10 cm and that the average vertical migration velocities of 137Cs and Pu are less than 0.2 cm y-1. The average accumulated depositions, deduced from the profile measurements, are 236 ±â€¯11 Bq.m-2 and 313 ±â€¯39 Bq.m-2 for 137Cs, 12.1 ±â€¯1.5 Bq.m-2 and 22.1 ±â€¯1.7 Bq.m-2 for 239+240Pu, and 1.23 ±â€¯0.46 Bq.m-2 and 1.58 ±â€¯0.60 Bq.m-2 for 238Pu, in Hiva Oa and Raivavae, respectively. The 238Pu/239+240Pu ratios are 0.102 ±â€¯0.050 at Hiva Oa and 0.072 ±â€¯0.033 at Raivavae. Both values are higher than the ratio in nuclear weapons tests fallout estimated to be 0.016 in 2016 (Hardy et al., 1973), because of the contribution of 238Pu fallout from SNAP-9A, which is latitude dependent. The 137Cs/239+240Pu ratios, 19.5 ±â€¯3.2 at Hiva Oa and 14.2 ±â€¯2.8 at Raivavae are in the lower part of the range of values observed in other regions of the world.

Are dietary reports in a case-control study on thyroid cancer biased by risk perception of Chernobyl fallout?

BACKGROUND: In retrospective case-control studies performed following nuclear tests or nuclear accidents, individual thyroid radiation dose reconstructions are based on fallout and meteorological data from the residential area, demographic characteristics, and lifestyle as well as dietary information. Collecting the latter is a controversial step, as dietary declarations may be affected by the subjects' beliefs about their risk behavior. This report analyses the potential for such bias in a case-control study performed in eastern France. METHODS: The study included 765 cases of differentiated thyroid carcinoma matched with 831 controls. Risk perceptions and beliefs of cases and controls were compared using Chi2 tests and differences in dietary reports were analyzed using a two-way ANOVA. RESULTS: In general, atmospheric pollution and living near a nuclear power plant were the two major risks that may influence thyroid cancer occurrence cited by cases and controls. When focusing in particular on the consequences of the Chernobyl accident, cases were more likely to think that the consequences were responsible for thyroid cancer occurrence than controls. Vegetable consumption during the two months after the Chernobyl accident was correlated with the status of subjects, but not to their beliefs. Conversely, consumption of fresh dairy products was not correlated with the status or beliefs of subjects. CONCLUSION: We found no evidence of systematic bias in dietary reports according to the status or beliefs held by subjects about the link between thyroid cancer occurrence and Chernobyl fallout. As such, these dietary reports may be used in further studies involving individual dosimetric reconstructions.

Reconstruction of individual thyroid doses to the Ukrainian subjects enrolled in the Chernobyl Tissue Bank.

The Chernobyl Tissue Bank (CTB) is an organisation that collects and stores samples of tumoral thyroid tissue obtained from Ukrainian and Russian subjects who were treated surgically for a thyroid cancer and had been exposed to (131)I from the Chernobyl accident. By 2012, the CTB had collected specimens of thyroid tissue from 2267 residents of Ukraine for the purpose of radiation research. Arithmetic mean thyroid doses and uncertainties have been estimated for all but 24 subjects for whom residence at the time of exposure was not found. The subjects have been classified into six groups or sub-groups according to the type of dosimetry-related information that is available for each of them. Excluding the 325 subjects with negligible radiation exposure, the arithmetic mean of the thyroid dose over all subjects is estimated as 0.4 Gy, with individual values ranging from <1 mGy to 13 Gy. The uncertainties in the individual thyroid dose estimates, characterised by the geometric standard deviations of their probability distributions, range from 1.3 to 8.7, with an arithmetic mean of 3.2.

Emergency Optically Stimulated Luminescence Dosimetry Using Different Materials.

Several materials were tested as possible individual emergency dosimeters using Optically Stimulated Luminescence (OSL) as means to assess the exposure. Materials investigated included human nails, business cards and plastic buttons. The OSL properties of these materials were studied in comparison with those of teeth. Most samples revealed OSL signals only after exposure to ionizing radiation; some samples of business cards, however, displayed a strong initial "native" signal (i.e. existing in the samples prior to irradiation). The sensitivity (minimum measurable dose) of the samples was found to vary significantly from sample to sample of the same material and was in the range from several tens of mGy to a few dozens of Gy. The dose response curves were linear for doses below 10 Gy. Fading of the OSL signals was estimated for different lenghts of times and found to be ~95%, 45%, 30% and 15% for samples of teeth, business cards, buttons and nails, respectively, following storage at room temperature in the dark for a period of 3 weeks after exposure. For samples stored under routine laboratory light, fading was much faster and the radiation-induced signals almost disappeared after a few hours of such illumination. It was concluded that the tested materials could be used in triage situations to detect and estimate the possible overexposure of individuals if the measurements can be performed soon enough after exposure.

Estimation of the thyroid doses for ukrainian children exposed in utero after the chernobyl accident.

This paper describes methods for estimating thyroid doses to Ukrainian children who were subjects of an epidemiological study of prenatal exposure and presents the calculated doses. Participants were 2,582 mother-child pairs in which the mother had been pregnant at the time of the Chernobyl accident on 26 April 1986 or in the 2-3 mo following when (131)I in fallout was still present. Among these, 1,494 were categorized as "exposed;" a comparison group of 1,088 was considered "relatively unexposed." Individual in utero thyroid dose estimates were found to range from less than 1 mGy to 3,200 mGy, with an arithmetic mean of 72 mGy. Thyroid doses varied primarily according to stage of pregnancy at the time of exposure and level of radioactive contamination at the location of residence. There was a marked difference between the dose distributions of the exposed and comparison groups, although nine children in the latter group had calculated doses in the range 100-200 mGy. For those children who were born after the accident and prior to the end of June 1986, postnatal thyroid doses were also estimated. About 7.7% (200) of the subjects received thyroid doses after birth that were at least 10% of their cumulative doses.

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel.

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, (60)Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was "typical" for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with "fast" (decay time around of 12 min) and "slow" (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure.

Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident.

BACKGROUND: Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose-response are poorly understood. METHODS: We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated (131)I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear-exponential functions. RESULTS: For thyroid doses <5 Gy, the dose-response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81-5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases. CONCLUSION: 10-15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.

Prevalence of hyperthyroidism after exposure during childhood or adolescence to radioiodines from the chornobyl nuclear accident: dose-response results from the Ukrainian-American Cohort Study.

Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of <0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses  =  0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n  =  5,767) and males (23 cases, n  =  6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR  =  1.86, P  =  0.06), but the statistical significance level was reduced (P  =  0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism.

Thyroid cancer following nuclear tests in French Polynesia.

BACKGROUND: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. METHODS: In a case-control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. RESULTS: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. CONCLUSION: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation.

Thyroid mass in children and adolescents living in the most exposed areas to Chernobyl fallout in Belarus.

This paper aims to determine the thyroid volumes in children and teenagers living in Gomel and Mogilev Oblasts, which are the areas of Belarus that were most affected by the Chernobyl accident. Results of thyroid volume measurements performed in 1991-1996 by the Sasakawa Memorial Health Foundation were used to evaluate the variation by age of the thyroid volumes for girls and boys aged from 5 to 16 y. Thyroid volumes for age groups without measurements were also estimated. For a given age and gender, the differences between children from Gomel and Mogilev Oblasts do not exceed 12 %, which is relatively small when the variability of individual values is considered. For children of a given age, the individual values show a variability characterised by geometric standard deviation (GSD) of 1.25-1.4. Values of thyroid mass that were derived from the measured thyroid volumes are being used within the framework of the on-going Belarusian-American cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident to estimate with more accuracy the thyroid doses that were received by the cohort members.

UV effects in tooth enamel and their possible application in EPR dosimetry with front teeth.

The effects of ultraviolet (UV) radiation on ionizing radiation biodosimetry were studied in human tooth enamel samples using the technique of electron paramagnetic resonance (EPR) in X-band. For samples in the form of grains, UV-specific EPR spectra were spectrally distinct from those produced by exposure to gamma radiation. From larger enamel samples, the UV penetration depth was determined to be in the 60-120 mum range. The difference in EPR spectra from UV exposure and from exposure to gamma radiation samples was found to be a useful marker of UV equivalent dose (defined as the apparent contribution to the gamma dose in mGy that results from UV radiation absorption) in tooth enamel. This concept was preliminarily tested on front teeth from inhabitants of the region of the Semipalatinsk Nuclear Test Site (Kazakhstan) who might have received some exposure to gamma radiation from the nuclear tests conducted there as well as from normal UV radiation in sunlight. The technique developed here to quantify and subtract the UV contribution to the measured tooth is currently limited to cumulative dose measurements with a component of UV equivalent dose equal to or greater than 300 mGy.

The utility of focus group interviews to capture dietary consumption data in the distant past: dairy consumption in Kazakhstan villages 50 years ago.

From 1949 to 1962, residents of several villages in Kazakhstan received substantial doses of radiation to the thyroid gland resulting from nuclear tests conducted at the Semipalatinsk Nuclear Test Site. The primary source of radiation was internal from an intake of radioactive iodine by consumption of contaminated dairy products. A previous research study of childhood exposure and thyroid disease in this region gathered limited data on study participants' dairy intake at the time of the fallout for the purpose of estimating past radiation doses. As many participants were too young at the time of the nuclear tests to recall dietary consumption and existing sources of archival data are limited, it was necessary to interview parents and other village residents who cared for children during this time - older adults ranging in age from 75 to 90 years. Results from 11 focus group interviews conducted in 2007 with 82 women from 4 villages in Kazakhstan yielded group-level estimates of age-, gender-, ethnicity- and village-specific dairy consumption patterns in rural Kazakhstan during the 1950s. Children typically consumed cow's milk with limited consumption of mare, goat and sheep milk; and consumed dairy products such as sour milk (airan), soft cottage cheese (tvorog) and fermented mare milk (koumiss) with the greatest amounts of koumiss reported at ages 15-21 years. The consumption patterns differed by age, and between Kazakh and Russian children, which should lead to different estimates of radiation exposure to the thyroid. This study showed the utility of focus groups to obtain quantitative estimates for dietary intake in the distant past.

Monte Carlo modeling of beta-radiometer device used to measure milk contaminated as a result of the Chernobyl accident.

This paper presents results of Monte Carlo modeling of the beta-radiometer device with Geiger-Mueller detector used in Belarus and Russia to measure the radioactive contamination of milk after the Chernobyl accident. This type of detector, which is not energy selective, measured the total beta-activity of the radionuclide mix. A mathematical model of the beta-radiometer device, namely DP-100, was developed, and the calibration factors for the different radionuclides that might contribute to the milk contamination were calculated. The estimated calibration factors for (131)I, (137)Cs, (134)Cs, (90)Sr, (144)Ce, and (106)Ru reasonably agree with calibration factors determined experimentally. The calculated calibration factors for (132)Te, (132)I, (133)I, (136)Cs, (89)Sr, (103)Ru, (140)Ba, (140)La, and (141)Ce had not been previously determined experimentally. The obtained results allow to derive the activity of specific radionuclides, in particular (131)I, from the results of the total beta-activity measurements in milk. Results of this study are important for the purposes of retrospective dosimetry that uses measurements of radioactivity in environmental samples performed with beta-radiometer devices.

A screening study of thyroid cancer and other thyroid diseases among individuals exposed in utero to iodine-131 from Chernobyl fallout.

BACKGROUND: Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. METHODS: We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother's thyroid (mean 72 mGy; range 0-3230 mGy). RESULTS: There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. CONCLUSION: Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy.

Ultrasound-detected thyroid nodule prevalence and radiation dose from fallout.

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

The Ukrainian-American study of leukemia and related disorders among Chornobyl cleanup workers from Ukraine: I. Study methods.

There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RADRUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of 111 were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects.

Contribution of internal exposures to the radiological consequences of the Chernobyl accident.

The main pathways leading to exposure of members of the general public due to the Chernobyl accident were external exposure from radionuclides deposited on the ground and ingestion of contaminated terrestrial food products. The collective dose to the thyroid was nearly 1.5 million man Gy in Belarus, Russia and Ukraine with nearly half received by children and adolescents. The collective effective dose received in 1986-2005 by approximately five million residents living in the affected areas of the three countries was approximately 50,000 man Sv with approximately 40% from ingestion. That contribution might have been larger if countermeasures had not been applied. The main radionuclide contributing to both external and internal effective dose is 137Cs with smaller contributions of 134Cs and 90Sr and negligible contribution of transuranic elements. The major demonstrated radiation-caused health effect of the Chernobyl accident has been an elevated incidence of thyroid cancer in children.

Uncertainties in individual doses in a case-control study of thyroid cancer after the Chernobyl accident.

Individual radiation doses to the thyroid were reconstructed for 2239 subjects of a case-control study of thyroid cancer among young people that was carried out in regions of Belarus and Russia contaminated by radioactive fallout from the Chernobyl accident. Although the process of dose reconstruction provides a point estimate of each subject's dose, it is obvious that there is uncertainty associated with these dose calculations. The following main sources of uncertainty in the estimated individual doses were identified: (1) shared and unshared errors associated with parameters of the dosimetry model; and (2) unshared errors that are associated with the variability, reliability and ability of information from the personal interviews. Besides setting up proper distributions for the parameters of the dosimetry model, inter-individual correlations were also defined to take into account shared errors. By the application of Monte Carlo simulations, a set of approximately log-normally distributed thyroid doses was obtained for each subject; the geometric standard deviations of the distributions are found to vary among individuals from 1.7 to 3.7.