COHERE - strengthening cooperation within the Canadian government on radiation research.

PURPOSE: Canadian Organization on Health Effects from Radiation Exposure (COHERE) is a government initiative to better understand biological and human health risks from ionizing radiation exposures relevant to occupational and environmental settings (<100 mGy, <6 mGy/h). It is currently a partnership between two federal agencies, Health Canada (HC) and the Canadian Nuclear Safety Commission (CNSC). COHERE's vision is to contribute knowledge to reduce scientific uncertainties from low dose and dose-rate exposures. COHERE will advance our understanding by bridging the knowledge gap between human health risks and linkages to molecular- and cellular-level responses to radiation. Research focuses on identifying sensitive, early, and key molecular events of relevance to risk assessment. CONCLUSIONS: The initiative will address questions of relevance to better apprize Canadians, including radiation workers and members of the public and Indigenous peoples, on health risks from low dose radiation exposure and inform radiation protection frameworks at a national and international level. Furthermore, it will support global efforts to conduct collaborative undertakings and better coordinate research. Here, we describe a historical overview of the research conducted, the strategic research agenda that outlines the scientific framework, stakeholders, opportunities to harmonize internationally, and how research outcomes will better inform communication of risk to Canadians.

Is there a role for the adverse outcome pathway framework to support radiation protection?

PURPOSE: In 2012, the Organization for Economic Cooperation and Development (OECD) formally launched the Adverse Outcome Pathway (AOP) Programme. The AOP framework has the potential for predictive utility in identifying early biological endpoints linked to adverse effects. It uses the weight of correlative evidence to identify a minimal set of measurable key events that link molecular initiating events to an adverse outcome. AOPs have the capability to identify knowledge gaps and priority areas for future research based on relevance to an adverse outcome. In addition, AOPs can identify pathways that are common among multiple stressors, thereby allowing for the possibility of refined risk assessments based on co-exposure considerations. The AOP framework is increasingly being used in chemical and ecological risk assessment; however, its use in the development of radiation-specific pathways has yet to be fully explored. To bring awareness of the AOP framework to the Canadian radiation community, a workshop was held in Canada in June 2018 that brought together radiation experts from Health Canada, the Canadian Nuclear Laboratories, and the Canadian Nuclear Safety Commission. METHODS: The purpose of the workshop was to share knowledge on the AOP framework, specifically (1) to introduce the concept of the AOP framework and its possible utility to Canadian radiation experts; (2) to provide examples on how it has advanced risk assessment; (3) to discuss an illustrative example specific to ionizing radiation; and lastly (4) to identify the broad benefits and challenges of the AOP framework to the radiation community. RESULTS: The participants showed interest in the framework, case examples were described and areas of challenge were identified. Herein, we summarize the outcomes of the workshop. CONCLUSIONS: Overall, participants agreed that by building AOPs in the radiation field, a network of data-sharing initiatives will enhance our interpretation of existing knowledge where current scientific evidence is minimal. They would provide new avenues to understand effects at low-dose and dose-rates and help to quantify the combined effect of multiple stressors on shared mechanistic pathways.

Evaluation of mean transit time of aerosols from the area of origin to the Arctic with 210Pb/210Po daily monitoring data.

In this study, the activity concentrations of 210Pb and 210Po on the 22 daily air filter samples, collected at CTBT Yellowknife station from September 2015 to April 2016, were analysed. To estimate the time scale of atmospheric long-range transport aerosol bearing 210Pb in the Arctic during winter, the mean transit time of aerosol bearing 210Pb from its origin was determined based on the activity ratios of 210Po/210Pb and the parent-progeny decay/ingrowth equation. The activity ratios of 210Po/210Pb varied between 0.06 and 0.21 with a median value of 0.11. The aerosol mean transit time based the activity ratio of 210Po/210Pb suggests longer mean transit time of 210Pb aerosols in winter (12 d) than in autumn (3.7 d) and spring (2.9 d). Four years 210Pb and 212Pb monitoring results and meteorological conditions at the Yellowknife station indicate that the 212Pb activity is mostly of local origin, and that 210Pb aerosol in wintertime are mainly from outside of the Arctic regions in common with other pollutants and sources contributing to the Arctic. The activity concentration ratios of 210Pb and 212Pb have a relatively constant value in summer with a significant peak observed in winter, centered in the month of February. Comparison of the 210Pb/212Pb activity ratios and the estimated mean 210Pb transit time, the mean aerosol transit times were real reflection of the atmosphere transport characteristics, which can be used as a radio-chronometer for the transport of air masses to the Arctic region.

Activity concentration measurements of selected radionuclides in seals from Canadian Arctic.

The activity concentrations of naturally occurring radionuclides (such as 226Ra, 210Pb and 210Po) and long lived 137Cs were measured in a total of 119 tissue samples (43 blubber, 43 liver, and 33 muscle samples) from 40 ringed seals and 4 bearded seals collected in the Arviat area of Canada during the fall of 2014. Activity concentration of 210Po was measured in all seal liver and muscle samples individually. The average 210Po activity concentrations were 25 ± 7.6 Bq/kg fresh weight (fw) in muscle and 211 ± 58 Bq/kg fw in liver for ringed seals, and 20 ± 6.1 Bq/kg fw in muscle and 231 ± 150 Bq/kg fw in liver for bearded seals. Due to insufficient sample material for most samples collected, gamma counting for radioactive caesium and radiochemical analysis for 226Ra and 210Pb were performed for pooled samples. Activity concentrations of 210Pb and 226Ra were generally below detection limits. While 134Cs activity concentration was not detectable, 137Cs activity concentration was detected in muscle and liver samples. On average, the 137Cs activity concentrations were 0.25 ± 0.05 and 0.12 ± 0.04 Bq/kg fw in muscle and liver samples of ringed seals, and 0.11 ± 0.02 and 0.10 ± 0.03 Bq/kg fw in muscle and liver samples of bearded seals, respectively. Neither 210Po nor 137Cs were detected in the blubber samples. This study confirmed that 210Po is the dominant contributor to radiation doses resulting from seal consumption. Man-made contaminant 137Cs only contributes less than 0.01% of the total ingestion dose obtained from Arviat seals.

GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK - SUMMARY OF THE SECOND EXERCISE.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency as a means of enhancing response capability, health outcomes and community resilience. GHSI partners conducted an exercise in collaboration with the WHO Radiation Emergency Medical Preparedness and Assistance Network and the IAEA Response and Assistance Network, to test the participating laboratories (18) for their capabilities in in vitro assay of biological samples, using a urine sample spiked with multiple high-risk radionuclides (90Sr, 106Ru, 137Cs, and 239Pu). Laboratories were required to submit their reports within 72 h following receipt of the sample, using a pre-formatted template, on the procedures, methods and techniques used to identify and quantify the radionuclides in the sample, as well as the bioassay results with a 95% confidence interval. All of the participating laboratories identified and measured all or some of the radionuclides in the sample. However, gaps were identified in both the procedures used to assay multiple radionuclides in one sample, as well as in the methods or techniques used to assay specific radionuclides in urine. Two-third of the participating laboratories had difficulties in determining all the radionuclides in the sample. Results from this exercise indicate that challenges remain with respect to ensuring that results are delivered in a timely, consistent and reliable manner to support medical interventions. Laboratories within the networks are encouraged to work together to develop and maintain collective capabilities and capacity for emergency bioassay, which is an important component of radiation emergency response.

A study on the effect of the internal exposure to (210)Po on the excretion of urinary proteins in rats.

This study was designed to assess the feasibility of a noninvasive urine specimen for the detection of proteins as indicators of internal exposure to ionizing radiation. Three groups of rats (five in each group) were intravenously injected with 1601 ± 376, 10,846 ± 591 and 48,467 ± 2812 Bq of (210)Po in citrate form. A sham-exposed control group of five rats was intravenously injected with sterile physiological saline. Daily urine samples were collected over 4 days following injection. Purification and pre-concentration of urinary proteins were carried out by ultrafiltration using a 3000 Da molecular weight cutoff membrane filter. The concentration of common urinary proteins, namely albumin, alpha-1-acid glycoprotein, immunoglobulins IgA and IgG, was measured by an enzyme-linked immunosorbent assay. Urinary excretion of albumin decreased dose-dependently (p < 0.05) 96 h post-injection relative to the control group. In contrast, no statistically significant effects were observed for other proteins tested. The dose-dependent decrease in urinary excretion of albumin observed in this study underscores the need for further research, which may lead to the discovery of new biomarkers that would reflect the changes in the primary target organs for deposition of (210)Po.

A study on the levels of radioactivity in fish samples from the experimental lakes area in Ontario, Canada.

To better understand background radiation levels in country foods, a total of 125 fish samples were collected from three lakes (Lake 226, Lake 302 and Lake 305) in the Experimental Lakes Area (ELA) in Ontario of Canada during the summer of 2014. Concentrations of naturally occurring radionuclides ((226)Ra, (210)Pb and (210)Po) as well as anthropogenic radionuclides ((134)Cs and (137)Cs) were measured. This study confirmed that (210)Po is the dominant contributor to radiation doses resulting from fish consumption. While concentrations of (210)Pb and (226)Ra were below conventional detection limits, (210)Po was measured in almost all fish samples collected from the ELA. The average concentration was about 1.5 Bq/kg fresh weight (fw). None of the fish samples analysed in this study contained any detectable levels of (134)Cs. An average (137)Cs level of 6.1 Bq/kg fw was observed in freshwater fishes harvested in the ELA, almost twice that of samples measured in the National Capital Region of Canada in 2014 and more than 20 times higher than the levels observed in marine fish harvested from the Canadian west coast in 2013 and 2014. However, it is important to note that the concentrations of (137)Cs in fish samples from these inland lakes are considered very low from a radiological protection perspective. The resulting radiation dose for people from fish consumption would be a very small fraction of the annual dose from exposure to natural background radiation in Canada. The results indicate that fishes from inland lakes do not pose a radiological health concern.

GHSI EMERGENCY RADIONUCLIDE BIOASSAY LABORATORY NETWORK: SUMMARY OF A RECENT EXERCISE.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop their collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency. A recent exercise was conducted to test the participating laboratories for their capabilities in screening and in vitro assay of biological samples, performing internal dose assessment and providing advice on medical intervention, if necessary, using a urine sample spiked with a single radionuclide, 241Am. The laboratories were required to submit their reports according to the exercise schedule and using pre-formatted templates. Generally, the participating laboratories were found to be capable with respect to rapidly screening samples for radionuclide contamination, measuring the radionuclide in the samples, assessing the intake and radiation dose, and providing advice on medical intervention. However, gaps in bioassay measurement and dose assessment have been identified. The network may take steps to ensure that procedures and practices within this network be harmonised and a follow-up exercise be organised on a larger scale, with potential participation of laboratories from the networks coordinated by the International Atomic Energy Agency and the World Health Organization.

Emergency Radiobioassay Method for Determination of 9°Sr and ²²6Ra in a Spot Urine Sample.

A new radiobioassay method has been developed for simultaneous determination of (90)Sr and (226)Ra in a spot urine sample. The method is based on a matrix removal procedure to purify the target radionuclides from a urine sample followed by an automated high performance ion chromatographic (HPIC) separation of (90)Sr and (226)Ra and offline radiometric detection by liquid scintillation counting (LSC). A Sr-resin extraction chromatographic cartridge was used for matrix removal and purification of (90)Sr and (226)Ra from a urine sample prior to its introduction to the HPIC system. The HPIC separation was carried out through cation exchange chromatography using methanesulfonic acid (75 mM) as the mobile phase at 0.25 mL/min flow rate. The performance criteria of the method was evaluated against the American National Standard Institute ANSI/HPS N13.30-2011 standard for the root mean squared error (RMSE) of relative bias (Br) and relative precision (SB) at two different spiked activity levels. The RMSE of Br and SB for (90)Sr and (226)Ra were found to be satisfactory (≤0.25). The minimum detectable activity (MDA) of the method for (90)Sr and (226)Ra are 2 Bq/L and 0.2 Bq/L, respectively. The MDA values are at least 1/10th of the concentrations of (90)Sr (190 Bq/L) and (226)Ra (2 Bq/L) excreted in urine on the third day following an acute exposure (inhalation) that would lead to an effective dose of 0.1 Sv in the first year. The sample turnaround time is less than 8 h for simultaneous determination of (90)Sr and (226)Ra.

Radon exhalation from sub-slab aggregate used in home construction in Canada.

Exposure to elevated levels of radon in homes has been shown to result in an increased risk of developing lung cancer. The two largest contributors to indoor radon are radon in soil gas, formed from the rocks and soil surrounding the home, and building materials such as aggregate. This study measured the surface radon exhalation rates for 35 aggregate samples collected from producers across Canada. The radon exhalation rates ranged from 2.3 to 479.9 Bq m(-2) d(-1), with a mean of 80.7±112 Bq m(-2) d(-1). Using a simple, conservative analysis, the aggregate contribution to radon concentrations in an unfinished basement was determined. The maximum estimated radon concentration was 32.5±2.7 Bq m(-3), or ~16 % of the Canadian Radon Guideline. It can be concluded that under normal conditions radon exhalation from aggregate contributes very little to the total radon concentration in indoor air.

EURADOS intercomparison on emergency radiobioassay.

Nine laboratories participated in an intercomparison exercise organised by the European Radiation Dosimetry Group (EURADOS) for emergency radiobioassay involving four high-risk radionuclides ((239)Pu, (241)Am, (90)Sr and (226)Ra). Diverse methods of analysis were used by the participating laboratories for the in vitro determination of each of the four radionuclides in urine samples. Almost all the methods used are sensitive enough to meet the requirements for emergency radiobioassay derived for this project in reference to the Clinical Decision Guide introduced by the NCRP. Results from most of the methods meet the requirements of ISO 28218 on accuracy in terms of relative bias and relative precision. However, some technical gaps have been identified. For example, some laboratories do not have the ability to assay samples containing (226)Ra, and sample turnaround time would be expected to be much shorter than that reported by many laboratories, as timely results for internal contamination and early decisions on medical intervention are highly desired. Participating laboratories are expected to learn from each other on the methods used to improve the interoperability among these laboratories.

An emergency radiobioassay method for 226Ra in human urine samples.

A new radioanalytical method was developed for rapid determination of (226)Ra in human urine samples. The method is based on organic removal and decolourisation of a urine sample by a polymeric (acrylic ester) solid phase sorbent material followed by extraction and preconcentration of (226)Ra in an organic solvent using a dispersive liquid-liquid microextraction technique. Radiometric measurement of (226)Ra was carried out using a liquid scintillation counting instrument. The minimum detectable activity for the method (0.15 Bq l(-1)) is lower than the required sensitivity of 0.2 Bq l(-1) for (226)Ra in human urine samples as defined in the requirements for radiation emergency bioassay techniques for the public and first responders based on the dose threshold for possible medical attention recommended by the International Commission on Radiological Protection (ICRP). The accuracy (expressed as relative bias, B(r)) and repeatability of the method (expressed as relative precision, S(B)) evaluated at the reference level (2 Bq l(-1)) were found to be -4.5 and 2.6 %, respectively. The sample turnaround time was <5 h for a single urine sample and <20 h for a batch of six urine samples. With the fast sample turnaround time combined with the potential to carry out the analysis in a field deployable mobile laboratory, the newly developed method can be used for emergency radiobioassay of (226)Ra in human urine samples following a radiological or nuclear accident.

Excretion of volatile ¹³¹I from rats following administration of Na¹³¹I or MIBG-¹³¹I.

Current practice for radiation protection associated with (131)I therapy mainly focuses on external and internal exposure caused by physical contamination of the hospital staff, other patients and family members. However, if volatile (131)I is excreted by the treated patients, these individuals could also be exposed through inhalation of (131)I. This study quantifies the amount of volatile (131)I excreted by rats after intravenous administration of metaiodobenzylguanidine (MIBG)-(131)I or Na(131)I, the two most common forms of (131)I therapy. The results indicate that in 4 d following administration, the total excretion of volatile (131)I was 0.036 and 0.17 % of the administered activities of MIBG-(131)I and Na(131)I, respectively. As administered activities for (131)I therapy are typically of the order of 1-10 GBq, the overall excretion of volatile (131)I from a patient can be as high as 20 MBq. As a result, a family member can receive up to 0.07 mSv committed effective dose from inhaling the volatile (131)I excreted by the patient.

Canada's efforts in developing capabilities in radiological population monitoring.

Population monitoring is an important component of radiological and nuclear emergency preparedness and response. Since 2002, Canada has been investing in developing national capabilities in radiological population monitoring. This paper summarizes Canada's efforts in developing methods and techniques in biological dosimetry and in vivo and in vitro bioassay techniques. There are still many gaps to fill that require further efforts. Integration of different monitoring methods and techniques in order to have the best assessment of radiation dose to support medical management and integration of Canada's efforts with international efforts are recommended.

Molecularly imprinted polymers for (90)Sr urine bioassay.

A molecularly imprinted polymer (MIP) comprising dicyclohexano-18-crown-6 (DCH18C6) was synthesized as a Sr-selective sorbent for urine bioassay purposes. MIP particles (326 ± 2 nm diameter) were formed using acetone and acetonitrile (1:3 v/v) as the porogen, methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The DCH18C6-MIP particles were impregnated with additional DCH18C6 and treated further with NaOH to attain better binding affinity for Sr(2+). The effects of pH, ionic strength and amount of particles were evaluated for optimal extraction of (90)Sr(2+) from urine samples, as measured by liquid scintillation analysis (LSA). After up to 94% of (90)Y was removed by precipitation with TiO(2), DCH18C6-MIP particles were applied for selective SPE of (90)Sr remaining in the urine matrix for final LSA.

International workshop on emergency radiobioassay: considerations, gaps and recommendations.

An international workshop on emergency radiobioassay was held in Ottawa, Canada, 1-3 September 2010. Sixty-five scientists and public health officials from five countries attended the workshop and gave 36 presentations. During the workshop, many considerations were raised, gaps identified, and recommendations given for emergency radiobioassay for both preparedness and response in case of a radiological or nuclear incident. In short, some bioassay methods and protocols need to be developed, validated, and exercised; national and international radiobioassay laboratory networks should be established; and communications and collaborations among public health officials, monitoring experts, and medical staff are encouraged. All these activities are required to make us better prepared for an RN emergency.

Preliminary studies of an 18-crown-6 ether modified magnetic cation exchange polymer in rapid (90)Sr bioassay.

A cation exchange polymer resin embedded with magnetic nanoparticles and modified with crown ether was developed for urinalysis to rapidly monitor levels of (90)Sr exposure in humans who have been involved in a nuclear event. Invention of the resin matrix of 2-acrylamido-2-methyl-1-propanesulfonic acid cross-linked with divinylbenzene incorporated a Sr(2+) chelating agent, di-tert-butyl-cyclohexano-18-crown-6 through surface immobilization using a molecular modifier 1-octanol. The performance of these magnetic cation exchange resin particles was investigated by separating (90)Sr in the presence of (90)Y progeny. Masking agents and precipitants were examined to ascertain that sodium hydroxide at pH 7.5 was capable of selectively removing 89 ± 2% (90)Y before subsequent (90)Sr uptake. Preliminary investigations in rapid urinalysis were successful in isolating 83 ± 2% (90)Sr when pH was optimized to 9, with a sample turnover time <2 h, which is promising for radiological emergencies.

Biokinetics of ²¹°Po in rats: excretion via urine and faeces and retention in tissues and organs.

Daily excretions of ²¹°Po from rats via urine and faeces following i.v. administration of polonium citrate, from Day 2 to Day 5, were reported, together with retentions in tissues and organs on Day 5. Emphasis is given to the methods of measurement and data quality rather than to the discussion of the observations. The authors aim to contribute data for developing or refining the biokinetic model for ²¹°Po metabolism.