Reduced lung function in children associated with cesium 137 body burden.

RATIONALE: We previously reported that obstructive and restrictive lung function findings were associated with radioactive Cesium 137 ((137)Cs) soil contamination from the 1986 Chernobyl disaster in a pediatric cohort residing in the Narodichesky district of Ukraine from 1993 to 1998. OBJECTIVES: To determine whether these associations persist, we repeated the study and refined the exposure by measuring individual radiation concentration with a whole-body counter. METHODS: Basic and post-bronchodilator spirometry measurements were made for 517 children aged 8 to 17 years born in and living within this differentially contaminated study area during 2008 to 2010. MEASUREMENTS AND MAIN RESULTS: A γ-spectrometer equipped with a collimator was used for the measurement of whole-body radiation and adjusted for weight. General linear and logistic regression models were used to estimate the association between spirometry measures and the weight-adjusted (137)Cs whole-body burden (Bq/kg) while controlling for potential confounders. The geometric median weight-adjusted radiation concentration was 65.96 Bq/kg (95% confidence interval, 14.98-240.9 Bq/kg), equivalent to a geometric mean internal dose estimate of 0.165 mSv/yr (95% confidence interval, 0.037-0.602 mSv/yr). Decrements in percentage predicted FEV1/FVC and an increased odds of bronchodilator responsiveness, restrictive impairment, and FVC less than lower limit of normal were associated with a log increase in weight-adjusted (137)Cs whole-body burden after adjusting for potential confounders. CONCLUSIONS: Our previous study of soil (137)Cs exposure and reduced lung function was corroborated herein with individual (137)Cs whole-body burden, although low, and annual internal dose data. Children in a region just outside of the closed Chernobyl contamination zone continued to have respiratory health deficits associated with (137)Cs whole-body burden as recently as 2010.

French contribution to develop Prussian blue.

PURPOSE: Prussian blue is an antidote indicated for the treatment of internal cesium radioisotope contamination. The French armed forces develop and manufacture some antidotal drugs meeting regulatory, analytical and pharmaceutical requirements in order to submit marketing authorization documentation. Prior to an initial meeting with the French National Agency for Medicines and Health Products Safety (ANSM) in 2011, the authors were following regulatory developments in free cyanide release, active pharmaceutical ingredient (API) synthesis, API specifications, ability of cesium/Prussian blue binding products and collection of pre-clinical data. MATERIALS AND METHODS: Free cyanide release was assessed by ultraviolet-visible (UV-Vis) spectrometry at 615 nm. The kinetics of cesium were evaluated in vitro by flame atomic absorption. Good laboratory practice (GLP) and mutagenic assays were examined in rat studies to assess 'no absorption'. RESULTS: A validated method makes it possible to assess the free cyanide in API according to the published tolerability in humans. The French synthesizer meets good manufacturing practice (GMP) to give a drug that is compliant with all specifications, ensuring its high quality. Two standard mutagenic assays showed mutagenic potential, leading to further tests to obtain more information on any induced chromosomal aberrations. Absorption could be an important factor in determining the risk posed by the drug. CONCLUSION: The French health service provides the country with several antidotal drugs reducing Chemical, Biological, Radiological and Nuclear (CBRN) risks. Using their GMP manufacturing facilities and pharmaceutical expertise, the French armed forces have contributed to developing drugs with marketing authorization, such as pentetate calcium trisodium (Ca-DTPA) for infusion, or under development with the French Alternative Energies and Atomic Energy Commission (CEA), such as Ca-DTPA by inhalation.

Quantitative measurement of cyanide released from Prussian Blue.

BACKGROUND: Prussian Blue (PB), ferric hexacyanoferrate is indicated for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide is 35-40% of PB's molecular composition, thus cyanide may be released during transit through the digestive tract under physiological pH. The U.S. Food and Drug Administration investigated the issue of cyanide release prior to drug approval to ensure the drug's benefits exceeded risks. OBJECTIVES: To determine cyanide released from PB under pH conditions that bracket human physiological exposure. METHODS: PB was incubated in situ at pH 1.0-12, 37 degrees C for 1-48 hours. Cyanide was measured using a validated colorimetric method by UV-VIS spectroscopy. RESULTS: PB had the highest cyanide release at pH 1 (135 ug/g) and lowest release at pH 5.0-7.0 from the highest daily dose of PB (17.5 g) (21 ug/g). Considering the minimal lethal dose of cyanide is approximately 50 mg, the maximal cyanide released (1.6 mg) does not present a safety concern.

Soluble or insoluble prussian blue for radiocesium and thallium poisoning?

OBJECTIVE: To review the available English-language literature concerning the efficacy of soluble and insoluble Prussian blue used as a therapeutic agent in radiocesium and thallium poisoning. DATA SOURCES: A thorough search of MEDLINE, Toxline, and EMBASE databases (1960s-August 2003) was performed. Search terms included Prussian blue, thallium, and radiocesium poisoning. Bibliographies of relevant papers were reviewed for additional citations. study selection AND DATA EXTRACTION: Reports and studies of human trials and cases, along with animal and relevant in vitro data, were sought. Data were categorized as insoluble and soluble Prussian blue and by thallium and radiocesium poisoning. DATA SYNTHESIS: The majority of evidence describing the efficacy of Prussian blue for radiocesium poisoning is based on the use of the insoluble form. In contrast, the majority of data supporting the efficacy of Prussian blue in thallium poisoning involves the use of the soluble form. CONCLUSIONS: Insoluble Prussian blue has recently been approved in the US for treatment of both thallium and radiocesium poisoning. While there is sufficient evidence that the insoluble form of Prussian blue is effective in radiocesium poisoning, there is a paucity of analogous data supporting its use in thallium poisoning. Whether the physicochemical differences between soluble and insoluble Prussian blue have any effect on outcomes in human poisoning is not known.

Prussian blue for treatment of radiocesium poisoning.

Prussian blue is a crystal lattice that exchanges potassium for cesium at the surface of the crystal. When given orally, it binds cesium that is secreted in the gut before it can be reabsorbed. Data suggest that in humans, Prussian blue can reduce cesium's half-life by approximately 43% and reduce total body burdens. Prussian blue is well tolerated at a dosage of 3 g/day with appropriate monitoring of serum potassium levels and observing for signs of constipation. Clinical data on the efficacy of Prussian blue in the management of radiocesium poisoning were evaluated. Articles published in English describing distribution and elimination of cesium in both humans and animals were reviewed, along with articles describing administration of Prussian blue in clinical toxicology.

Studies of any toxicological effects of Prussian blue compounds in mammals--a review.

The Chernobyl nuclear reactor accident, which resulted in widespread contamination with radiocaesium, led to studies of the use of Prussian Blue (PB) compounds as a countermeasure to reduce the caesium-137 and caesium-134 content of animal products. An important consideration in the practical use of PB compounds in agriculture is their possible toxicity. Hence it is pertinent to assess the work undertaken with laboratory rodents, domesticated animals and humans that has included studies of any toxic effects. Such studies showed that PB compounds had no adverse effects on animal health and production and, in addition, no toxic effects were noted in humans when PB was used experimentally or therapeutically.