Irina Guseva Canu

Cancer risk in nuclear workers occupationally exposed to uranium-emphasis on internal exposure.

Workers involved in the nuclear fuel cycle have a potential for internal exposure to uranium. The present review of epidemiological studies of these workers aims to elucidate the relationship between occupational internal uranium exposure and cancer risk. Eighteen cohort and 5 nested case-control studies published since 1980 are reviewed. Workers occupationally exposed to uranium appear to be at increased risk of mortality from neoplasms of the lung, larynx, and lymphatic and haematopoietic tissue. Currently available evidence for a positive association between internal exposure to uranium and the risk of cancer is limited. The common weaknesses in reviewed studies include low statistical power and inaccurate assessment of internal exposure to uranium. Further investigations should focus on precise assessment of occupational exposure and address the issue of potential confounders.

Health effects of naturally radioactive water ingestion: the need for enhanced studies.

Background: Radiological pollution is a potentially important aspect of water quality. However, relatively few studies have been conducted to document its possible health effects. Objective: In this commentary we discuss available epidemiological findings and related data from experimental studies concerning the health effects of naturally radioactive water ingestion. Discussion: Despite modest epidemiological evidence of uranium nephrotoxicity and radium effects on bone, available data are not sufficient to quantify the health effects of naturally occurring radionuclides in water. Methodological limitations (exposure measurement methods, control for confounding, sample size) affect most studies. Power calculations should be conducted before launching new epidemiological studies focusing on late pathological outcomes. Studies based on biomarkers of exposure and adverse effects may be helpful but should involve more specific molecules than biomarkers used in previous studies. Experimental data on ingestion of drinking water are limited to uranium studies, and there is some disagreement between these studies about the nephrotoxicity threshold. Conclusion: Further experimental and enhanced epidemiological studies should help to reduce uncertainties resulting from dose estimation to dose–response characterization.

Does uranium induce circulatory diseases? First results from a French cohort of uranium workers

Objectives Increased risk of circulatory system diseases (CSDs) was observed in nuclear workers handling uranium and plutonium in Russia and the UK. This work examines the CSD mortality after chronic intake of uranium among 2897 workers (79 892 person-years) at a uranium processing plant (1960–2006) in France. Methods Cumulative exposure to different uranium compounds, classified by their isotopic composition and solubility type, was quantified on the basis of a plant-specific job-exposure matrix and individual job histories. HRs and associated 95% CI for CSD (n=111) and specific CSD categories were estimated using Cox regression models, stratified on sex and birth cohort and adjusted for potential confounders. The effect of smoking was analysed among 260 smokers (42 CSD deaths). Results Compared to unexposed workers, CSD mortality was increased among workers exposed to slowly soluble reprocessed uranium (RPU) (HR=2.13, 95% CI=0.96 to 4.70) and natural uranium (HR=1.73, 95% CI=1.11 to 2.69). The risk increased with cumulative exposure and exposure duration. In the subgroup of smokers, the risk estimates were higher but with larger CIs: HR=1.91 (95% CI=0.92 to 3.98) for natural uranium and HR=4.78 (95% CI=1.38 to 16.50) for RPU. Conclusions The authors observed that exposure to slowly soluble uranium, namely RPU, may increase the risk of CSD mortality. However, these results are preliminary since the study is lacking statistical power and many other biological and lifestyle-related factors may cause CSD. More detailed investigations are necessary to confirm these findings and analyse in depth the effects of internal radiation exposure on the circulatory system.

Mortality (1968–2008) in a French cohort of uranium enrichment workers potentially exposed to rapidly soluble uranium compounds

Objectives Until recently, enrichment of uranium for civil and military purposes in France was carried out by gaseous diffusion using rapidly soluble uranium compounds. We analysed the relationship between exposure to soluble uranium compounds and exposure to external γ-radiation and mortality in a cohort of 4688 French uranium enrichment workers who were employed between 1964 and 2006. Methods Data on individual annual exposure to radiological and non-radiological hazards were collected for workers of the AREVA NC, CEA and Eurodif uranium enrichment plants from job-exposure matrixes and external dosimetry records, differentiating between natural, enriched and depleted uranium. Cause-specific mortality was compared with the French general population via standardised mortality ratios (SMR), and was analysed via Poisson regression using log-linear and linear excess relative risk models. Results Over the period of follow-up, 131 161 person-years at risk were accrued and 21% of the subjects had died. A strong healthy worker effect was observed: all causes SMR=0.69, 95% CI 0.65 to 0.74. SMR for pleural cancer was significantly increased (2.3, 95% CI 1.06 to 4.4), but was only based on nine cases. Internal uranium and external γ-radiation exposures were not significantly associated with any cause of mortality. Conclusions This is the first study of French uranium enrichment workers. Although limited in statistical power, further follow-up of this cohort, estimation of internal uranium doses and pooling with similar cohorts should elucidate potential risks associated with exposure to soluble uranium compounds.

REPROCESSED URANIUM EXPOSURE AND LUNG CANCER RISK

This study investigated the risk of lung cancer in regards to protracted occupational exposure to reprocessed uranium compounds. Two thousand seven hundred and nine male workers employed at the AREVA NC uranium processing plant between 1960 and 2005 in France were included in the cohort. Historical exposure to reprocessed uranium compounds classified by their solubility type was assessed on the basis of the plants specific job-exposure matrix. Cox proportional hazard models adjusted for attained age, calendar period, and socioeconomic status were used to estimate relative risks in regards of each type of uranium compound. The relative risk of lung cancer tended to increase with decreasing solubility of reprocessed uranium compounds. The highest—though not statistically significant—relative risk was observed among workers exposed to slowly soluble reprocessed uranium dioxide. This study is the first suggesting an increasing risk of lung cancer associated with exposure to reprocessed uranium. Our results are consistent with data from experimental studies of biokinetics and the action mechanism of slowly soluble uranium compounds, but need to be confirmed in larger studies with more detailed dose-response analyses.

Assessing the protection of the nanomaterial workforce

Abstract Responsible development of any technology, including nanotechnology, requires protecting workers, the first people to be exposed to the products of the technology. In the case of nanotechnology, this is difficult to achieve because in spite of early evidence raising health and safety concerns, there are uncertainties about hazards and risks. The global response to these concerns has been the issuance by authoritative agencies of precautionary guidance to strictly control exposures to engineered nanomaterials (ENMs). This commentary summarizes discussions at the “Symposium on the Health Protection of Nanomaterial Workers” held in Rome (25 and 26 February 2015). There scientists and practitioners from 11 countries took stock of what is known about hazards and risks resulting from exposure to ENMs, confirmed that uncertainties still exist, and deliberated on what it would take to conduct a global assessment of how well workers are being protected from potentially harmful exposures.

Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides

Background: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles—particularly through inhalation—occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose–response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. Methods: We conducted a case–control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. Results: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)—adjusted for external radiation, socioeconomic status, and smoking—was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (−1.9, 18) for uranium. Conclusions: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors. See video abstract at, http://links.lww.com/EDE/B232.

Nano- and neurotoxicology: an emerging discipline

Graphical abstract Figure. No caption available. HighlightsAvailable evidence suggests incomplete effectiveness of brain protective barriers against nanoparticles.Nanoparticles from continuously growing industrial production and the use of nanoparticles may impact human brain health.There is a need of original dedicated experimentalmodels and tools combining nanotoxicology and neurology research areas. Epidemiological studies dedicated to neurodegenerativediseases in manufactured nanoparticle‐exposed populations are needed.This novel discipline combining neuro and nanotoxicology is essential to study the interactions of nanoparticles and brain. ABSTRACT The present critical review analyzes the question of how nanoparticles from continuously growing industrial production and use of nanomaterials may impact human brain health. Available evidence suggests incomplete effectiveness of protective barriers of the brain against nanoparticles translocation to the brain. This raises concerns of potential effects of manufactured nanoparticles on brain functions, given that nanoparticles potential to induce oxidative stress, inflammation, death by apoptosis, or changes in the level of expression of certain neurotransmitters. Most concerns have not been studied sufficiently and many questions are still open: Are the findings in animals transposable to humans? What happens when exposure is chronic or protracted? What happens to the developing brain when exposure occurs in utero? Are some nanoparticles more deleterious, given their ability to alter protein conformations and aggregation? Aside from developments in nanomedicine, the evidence already available fully justifies the need to specifically evaluate the interactions between nanoparticles and the nervous system. The available data clearly indicates the need for original dedicated experimental models and tools for neurotoxicological research on the one hand, and the need for epidemiological studies of neurodegenerative diseases in manufactured nanoparticle‐exposed populations, on the other. A combination of nanotoxicology with neurology in a novel discipline, with its specific tools and methods of investigation, should enable answering still unresolved questions.

Suicide Among Farmers in France: Occupational Factors and Recent Trends.

ABSTRACT Numerous studies have found agricultural workers, including farmers, at elevated risk of suicide, and socioeconomic conditions have been suggested as one of the important determinants of this mortality cause. The real agricultural income per worker in Europe increased steadily from 2005 to 2007 and then fell by 1.8% in 2008 and by 11.6% in 2009. This drop was particularly pronounced in France. Repeated cross-sectional studies were conducted to investigate suicide mortality rates among French farmers in 2007–2009. The study population included all French farmers enrolled yearly in the compulsory Agricultural Social Security and Health Insurance (CCMSA). Most of the mean of 500,164 subjects per year were men (68%). National cause-specific mortality rates were used to calculate standardized mortality ratios (SMRs) and associated 95% confidence intervals (95% CIs) for both genders and for each of the 3 years. During the 3-year study period, 2,769 men and 997 women died. Suicide accounted for 417 of the men’s (15%) and 68 of the women’s (6.8%) deaths. Hanging was the most frequent method of suicide for both. Compared with the general population, the increased rate of suicide deaths among male farmers was 28% in 2008 and 22% in 2009. This increased rate was particularly high among those aged 45–54 years (31%) and 55–64 years (47%) in 2008 (and in the 55–64-year-old group in 2009 (64%). Two specific types of farming activity were associated with increased suicide mortality rates in both 2008 and 2009: dairy cattle farming (SMR = 1.56 [95% CI: 1.09–2.15] and SMR=1.47 [95% CI: 1.01–2.04]) and beef cattle farming (SMR = 2.27 [95% CI: 1.59–3.10] and SMR = 1.57 [95% CI: 1.01–2.27]). These results may be useful for a better understanding of the situation from an epidemiological standpoint and for improving suicide prevention policies in this particular population.

Methodological, political and legal issues in the assessment of the effects of nanotechnology on human health

Engineered nanomaterials (ENMs) raise questions among the scientific community and public health authorities about their potential risks to human health. Studying a prospective cohort of workers exposed to ENMs would be considered the gold standard for identifying potential health effects of nanotechnology and confirming the ‘no effect’ levels derived from cellular and animal models. However, because only small, cross-sectional studies have been conducted in the past 5 years, questions remain about the health risks of ENMs. This essay addresses the scientific, methodological, political and regulatory issues that make epidemiological research in nanotechnology-exposed communities particularly complex. Scientific challenges include the array of physicochemical parameters and ENM production conditions, the lack of universally accepted definitions of ENMs and nanotechnology workers, and the lack of information about modes of action, target organs and likely dose–response functions of ENMs. Standardisation of data collection and harmonisation of research protocols are needed to eliminate misclassification of exposures and health effects. Forming ENM worker cohorts from a combination of smaller cohorts and overcoming selection bias are also challenges. National or international registries for monitoring the exposures and health of ENM workers would be helpful for epidemiological studies, but the creation of such a registry and ENM worker cohorts will require political support and dedicated funding at the national and international levels. Public authorities and health agencies should consider carrying out an ENM awareness campaign to educate and engage all stakeholders and concerned communities in discussion of such a project.