A case-control study of thallium exposure with the risk of premature ovarian insufficiency in women.

Thallium exposure has been associated with female reproductive health, but little is known about its potential association with premature ovarian insufficiency (POI). In this study, a total of 169 patients with POI and 209 healthy women were recruited from Zhejiang province, China. Urinary thallium concentrations were significantly positively associated with the risk of POI [adjusted odds ratio (OR) = 1.63, 95% CI: 1.25-2.13, p < 0.001], geometric mean values of which were significantly higher in POI cases (0.213 µg/L, 0.302 µg/g for creatinine adjustment) than those of controls (0.153 µg/L, 0.233 µg/g for creatinine adjustment). Furthermore, the serum levels of follicle-stimulating hormone and luteinizing hormone were positively associated with urinary thallium concentrations, whereas anti-Mullerian hormone and estradiol were negatively correlated with thallium. To the best of our knowledge, this is the first study to provide evidence that thallium exposure at currently environmental levels is the potential risk factor for POI in women.

Thallium exposure at low concentration leads to early damage on multiple organs in children: A case study followed-up for four years.

Thallium (TI) is one of the most toxic heavy metals and priority pollutant metals. The emerging TI environmental pollution worldwide has posed a great threat to human health. However, based on the World Health Organization (WHO), the risk and severity of adverse health effects of TI in the range of 5-500 µg/L are uncertain. Moreover, evidence regarding the adverse impacts of TI on children's health is still insufficient. Herein, we aim to investigate the early adverse effects of TI on children's health and provide references for the WHO to establish stricter safety limits of TI. From 2015 to 2019, urinary TI and many clinical laboratory parameters related to blood routine, hepatic, renal, myocardial, coagulation function and serum electrolyte were measured in six children aged 1-9 years. The urinary TI concentration ranged from 13.4 µg/L to 60.1 µg/L with a mean of 36.1 µg/L and a median of 34.8 µg/L in six children in 2015. Although only four children felt a little poor appetite, several laboratory abnormalities indicated early damage in liver, renal, and myocardial functions in all children in 2015. After treatment and following up for four years, although the children's TI concentration decreased below 5 µg/L, their liver and renal functions did not completely recover, and their myocardial function worsened. Results indicated that impaired liver, renal, and myocardial functions were closely associated with elevated urinary TI concentration in children. Considering the increasing use of TI in high-technology industries and emerging TI environmental-contamination zones worldwide, establishing stricter safety limits of TI and paying more attention to the adverse health effects of TI on children are urgently required. SUMMARY: We found that a relatively low concentration of thallium (13.4 µg/L to 60.1 µg/L) impaired liver, renal, and myocardial function in six children. After treatment and following up these children for four years, although their urinary TI concentration decreased below 5 µg/L, their liver and renal functions did not completely recover, and their myocardial function worsened.

Toxicity of Thallium at Low Doses: A Review.

A mini review of the toxicity of Thallium (Tl) at low doses is herein presented. Thallium has severe toxicity. Although its acute biological effects have been widely investigated and are well known, its biological effects on human health and in cell cultures at low doses (<100 µg/L) due, for example, to Tl chronic exposure via consumption of contaminated water or foods, have often been overlooked or underestimated. Relatively few papers have been published on this topic and are herein reviewed to provide a focused scientific opinion in the light of current worldwide regulatory issues.

Metal concentrations in surface water and sediments from Pardo River, Brazil: human health risks.

Pardo River (Brazil) is suffering from an important anthropogenic impact due to the pressure of highly populated areas and the influence of sugarcane cultivation. The objective of the present study was to determine the levels of 13 trace elements (As, Be, Cd, Cr, Cu, Pb, Mn, Hg, Ni, Tl, Sn, V and Zn) in samples of surface water and sediments from the Pardo River. Furthermore, the human health risks associated with exposure to those metals through oral intake and dermal absorption were also evaluated. Spatial and seasonal trends of the data were closely analyzed from a probabilistic approach. Manganese showed the highest mean concentrations in both water and sediments, remarking the incidence of the agricultural activity and the geological characteristics within the basin. Thallium and arsenic were identified as two priority pollutants, being the most important contributors to the Hazard Index (HI). Since non-carcinogenic risks due to thallium exposure slightly exceeded international guidelines (HI>1), a special effort should be made on this trace element. However, the current concentrations of arsenic, a carcinogenic element, were in accordance to acceptable lifetime risks. Nowadays, there is a clear increasing growth in human population and economic activities in the Pardo River, whose waters have become a serious strategic alternative for the potential supply of drinking water. Therefore, environmental monitoring studies are required not only to assure that the current state of pollution of Pardo River does not mean a risk for the riverside population, but also to assess the potential trends in the environmental levels of those elements.

Associations of multiple metals with kidney outcomes in lead workers.

OBJECTIVES: Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal coexposure on kidney function. Therefore, the authors evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers. METHODS: Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures and ln-urine N-acetyl-ß-D-glucosaminidase (NAG). RESULTS: In 684 participants, median urine thallium and antimony were 0.39 and 0.36 µg/g creatinine, respectively. After adjustment for lead dose, urine creatinine and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate; associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based estimates of glomerular filtration rate =5.2 ml/min/1.73 m2; 95% CI =2.4 to 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium. CONCLUSIONS: Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.

Clinical evaluation of desferrioxamine (DFO) for removal of thallium ions in rat.

An investigation was conducted to evaluate the ability of DFO following the administration of thallium salt in male Wistar rats. Thallium was introduced to several groups of weanling male Wistar rats via different means, through drink, food and intraperitoneal injection. A control group was fed on a diet containing a normal level of iron. After a period of 30 days, all the rats administered thallium were severely anemic and showed toxicity symptoms through loss of hair, an increase in thallium and a decrease in iron levels in the blood. Chelation therapy was carried out to remove the toxic element from the body. The ability of desferrioxamine (DFO) in removing thallium was investigated by injection of this chelator for one week to the remaining rats of similar groups. The results showed that the thallium level present in the blood was significantly reduced and, at the same time, the iron concentration returned to the normal level. It was concluded that DFO chelator is able to remove thallium from the body and could be used for the treatment of complications and eradication of symptoms of thallium intoxication.

Toxic neuropathies associated with pharmaceutic and industrial agents.

Neuropathies associated with industrial, environmental, and pharmacologic toxicants are uncommon. Nevertheless, it is important to consider toxic etiologies in the differential diagnosis of neuropathies, because they are among the most treatable forms of peripheral nervous system dysfunction. The purpose of this article is to discuss the clinical investigation of a suspected toxic neuropathy, to review some of the more common or representative neurotoxicants, and to identify the methods for establishing causation.

[Sustainability of medical imaging in cardiology]. / La sostenibilità della diagnosi per immagini in cardiologia.

Every year, 5 billion imaging testing are performed worldwide, and about 1 out of 2 are cardiovascular examinations. According to recent estimates, 30 to 50% of all examinations are partially or totally inappropriate. This represents a potential damage for patient undergoing imaging (who takes the acute risks of a stress procedure and/or a contrast study without a commensurable benefit), an exorbitant cost for the society and an excessive delay in the waiting lists for other patients needing the examination. Economic induction, medico-legal concern, and specialist guidelines, which do not quantitate the potential benefits against the risks of a given procedure, boost inappropriateness of all imaging techniques. In case of ionizing tests, the reduction of useless imaging testing would improve the quality of care also through abatement of long-term risks, which are linked to the dose employed. The radiation dose equivalent of common cardiological imaging examinations corresponds to more than 1000 chest x rays for a thallium scan and to more than 500 chest x-rays for a multislice computed tomography. Although a direct evaluation of incidence of cancer in patients submitted to these procedures is not available, the estimated risk (often ignored by cardiologists) of cancer according to the latest 2005 Biological Effects of Ionizing Radiation Committee VII is about one in 500 exposed patients for a Thallium scintigraphy scan, and one in 750 for a CT scan. Such a risk is probably not acceptable when a scintigraphic or radiological procedure is applied for mass screening (when the risk side of the risk-benefit balance is not considered) or when a similar information can be obtained by other means. By contrast, it is fully acceptable in appropriately selected groups as a filter to more invasive, risky and costly procedures (for instance, coronary angiography and anatomy-driven revascularization). At this point, the cardiological community, that faces the reality of limited resources, should do every effort in order to minimize inappropriate testing, since they induce an exorbitant increase in health care costs with no improvement, and possibly with a reduction in care quality.

Sodium bicarbonate-augmented stress thallium myocardial scintigraphy.

It is well known that sodium bicarbonate in pharmacological doses induces transient alkalosis, causing intracellular transport of serum potassium. The aims of this study were (a) to investigate whether, in humans, myocardial thallium-201 uptake can be augmented by pretreatment with a single bolus of sodium bicarbonate at a pharmacological dose, (b) to verify general safety aspects of the intervention and (c) to evaluate the clinical implications of augmentation of (201)Tl uptake, if any. Routine exercise myocardial scintigraphy was performed twice in eight adult volunteers (five normal and three abnormal), once without intervention and the second time (within a week) following intravenous administration of sodium bicarbonate (88 mEq in 50 ml) as a slow bolus 1 h prior to the injection of (201)Tl. Conventional myocardial thallium study was compared with sodium bicarbonate interventional myocardial scintigraphy with respect to myocardial uptake (counts per minute per mCi injected dose), washout patterns in normal and abnormal myocardial segments, and overall clinical interpretation based on planar and single-photon emission tomographic (SPET) images. All patients remained asymptomatic after the intervention. A mean increase of 53% in myocardial uptake of thallium was noted in post-exercise acquisitions after the intervention, confirming uptake of the tracer via the potassium-hydrogen pump and its augmentation by transient alkalosis. The washout pattern remained unchanged. The visual quality of planar and SPET images improved significantly after the intervention. Out of the five abnormal myocardial segments identified in three cases, four showed significant filling-in after the intervention, causing the diagnosis to be upgraded from "partial scar" to "ischaemia", or from "ischaemia" to "normal". The overall scan impression changed in two out of three such cases. Sodium bicarbonate augmentation may have significant implications for stress-thallium scintigraphy and may be a new parameter for defining myocardial viability.

Influencias de medidas regulatorias en la morbilidad y mortalidad por Talio y Parathion en Rosario, Argentina / The influence of regulatory steps in the morbility and mortality due to thallium and parathion in Rosario, Argentina

La expanción en el uso de plaguicidas en los últimos 50 años ha sido acompañada por la introducción de regulaciones tendientes a garantizar la seguridad de usuarios, consumidores y medio ambiente. El objeto de este trabajo es mostrar la disminución o supresión de las intoxicacionespor talio y parathion atendidas en Rosario luego de las medidas de prohibición del uso de dichos plaguicidas. En una revisión sobre 1343 intoxicaciones agudas con plaguicidas atendidas en Rosario entre 1977 y 1985, el 25,5 por ciento corresponde a pacientes intoxicados con talio de raticidas (desde 32,6 por ciento en 1977 hasta 7,1 por ciento en 1985) y luego practicamente desaparecen ( la última intoxicación registrada ocurrió en 1990). Nueve de los 10 casos letales por AP entre 1977 y 1985 y 8 de 11 casos letales por AP en el período 1990-1994 corresponden a intoxicacion por parathion. La última intoxicación por talio representaron un problema sanitario grave no sólo por su elevada incidencia sino tambien por la complejidad de los cuadros clínicos y la dudosa eficacia de las medidas terapéuticas disponibles. La gravedad de las intoxicaciones por parathion determinaron la inclusión de variantes en el tratamiento. En las dos situaciones consideradas, la prohibición de su uso determinó un rápido descenso en la morbilidad y mortalidad y las sustancias alternativas a su uso (anticuagulantes y otros compuestos organofosforados anticolinesterasa), si bien no son inocuas, tienen un margen de seguridad más aceptable incluyendo el uso inapropiado(AU)

Influencias de medidas regulatorias en la morbilidad y mortalidad por Talio y Parathion en Rosario, Argentina / The influence of regulatory steps in the morbility and mortality due to thallium and parathion in Rosario, Argentina

La expanción en el uso de plaguicidas en los últimos 50 años ha sido acompañada por la introducción de regulaciones tendientes a garantizar la seguridad de usuarios, consumidores y medio ambiente. El objeto de este trabajo es mostrar la disminución o supresión de las intoxicacionespor talio y parathion atendidas en Rosario luego de las medidas de prohibición del uso de dichos plaguicidas. En una revisión sobre 1343 intoxicaciones agudas con plaguicidas atendidas en Rosario entre 1977 y 1985, el 25,5 por ciento corresponde a pacientes intoxicados con talio de raticidas (desde 32,6 por ciento en 1977 hasta 7,1 por ciento en 1985) y luego practicamente desaparecen ( la última intoxicación registrada ocurrió en 1990). Nueve de los 10 casos letales por AP entre 1977 y 1985 y 8 de 11 casos letales por AP en el período 1990-1994 corresponden a intoxicacion por parathion. La última intoxicación por talio representaron un problema sanitario grave no sólo por su elevada incidencia sino tambien por la complejidad de los cuadros clínicos y la dudosa eficacia de las medidas terapéuticas disponibles. La gravedad de las intoxicaciones por parathion determinaron la inclusión de variantes en el tratamiento. En las dos situaciones consideradas, la prohibición de su uso determinó un rápido descenso en la morbilidad y mortalidad y las sustancias alternativas a su uso (anticuagulantes y otros compuestos organofosforados anticolinesterasa), si bien no son inocuas, tienen un margen de seguridad más aceptable incluyendo el uso inapropiado

Evaluation of diabetic patients for renal and pancreas transplantation: noninvasive screening for coronary artery disease using radionuclide methods.

Pharmacologic stress thallium scintigraphy is commonly performed in the risk assessment of diabetic patients with nephropathy before kidney and/or pancreas transplantation; however, controversy exists regarding the test's accuracy in detecting coronary artery disease. Our purpose was to compare pharmacologic stress thallium scintigraphy and also exercise radionuclide ventriculography with coronary angiography in diabetic patients undergoing evaluation for transplantation. In addition, we also determined the association of the test results with outcome after transplantation. The medical records of 47 patients (mean age, 37+/-9 years) without clinical evidence of coronary artery disease were reviewed. Forty-one patients had pharmacologic stress thallium scintigraphy performed during their evaluation. Sensitivity was 62% and specificity was 76% for detecting > or = 75% coronary artery stenosis (sensitivity was 53% and specificity was 73% for > or = 50% stenosis). Thirty-five patients had exercise radionuclide ventriculography performed. Sensitivity was 50% and specificity was 67% for detecting > or = 75% coronary artery stenosis (sensitivity was 44% and specificity was 63% for > or = 50% stenosis). Thirty patients had both pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography performed; when either test was abnormal, sensitivity in the detection of > or = 50% or > or = 75% stenosis tended to increase compared with pharmacologic stress thallium scintigraphy alone (0.05

Chronic administration of malonic acid produces selective neural degeneration and transient changes in calbindin immunoreactivity in rat striatum.

Adult rats received chronic dialytic delivery devices that exposed the striatum to a 100 mM, 400 mM, or 4 M solution of the reversible succinate dehydrogenase inhibitor malonic acid (MA). Three weeks of exposure to 100 or 400 mM MA produced no significant reduction in striatal cytochrome oxidase staining, whereas striata chronically exposed to 1 and 4 M MA showed a significant and dose-related reduction in cytochrome oxidase staining. In striata exposed to 1 M MA, analysis of regions radial to the necrotic core revealed significant reduction of nissl cell staining with relative sparing of NADPH-diaphorase-containing neurons. Although 100 and 400 mM MA failed to produce lesions, both of these concentrations significantly decreased the number of striatal calbindin (CALB) immunoreactive perikarya. The reduction in CALB immunoreactivity was partly reversed in animals allowed to survive 4 weeks after cessation of exposure to 400 mM MA. These results indicate that, like striatal lesions produced by quinolinic acid, lesions produced by chronic exposure to MA possess a Huntington's disease-like pattern of selective neurodegeneration. In addition, exposure to subthreshold MA concentrations (100 and 400 mM) produce widespread transient changes in striatal CALB that may be associated with a premorbid state of neuronal dysfunction.

Electroretinography in the diagnosis of thallium intoxication.

Appearance of dystrophic alterations in the retina was carried out by administering 0.2 ml 12 mM of tallium chloride solution into the vitreous humour of 9 rabbits. Electroretinographic examination revealed a decline in the b wave either decreasing 2-3 times or entirely disappearing as early as on day 2 after the administration of tallium chloride. Electron microscopic investigation suggested that photoreceptors of the retina were initial by involved in the pathological process. Namely, the external segments of the photoreceptors were found to be reduced, indicating impairment of the formation of photoreceptor disks, which is known to proceed continuously under normal conditions. In the absence of an electroretinogram (ERG), the photoreceptor layers were shown to have disappeared completely. An examination of 28 subjects who were exposed to tallium and its compound at work revealed impaired retinal electrogenesis, as evident from subnormal ERG responses. This was of a functional nature and became more pronounced as occupational exposure time increased. The fact that the internal retinal layers and the 3-rd neurone remained intact, as suggested by the electrical sensitivity of the eye and lability of the optic nerve as well as by static perimetry, correlated with the EM findings obtained in experiments. Ophthalmobiomicroscopic examination of 12 eyes yielded data on characteristic changes in the lens when visual functions remained intact. These findings suggest that changes in the ERG may be indicative of initial preclinical symptoms of tallium intoxication and as such can be used when persons exposed to it in industry receive check-ups.

Evaluación epidemiológica de riesgos causados por agentes químicos ambientales: Generalidades y toxicología

Contiene: Evaluación del riesgo en la exposición a sustancias tóxicas - - Identificación de las principales fuentes contaminantes del ambiente: monóxido de carbono, dióxido de azufre, oxidos de nitrógeno, hidrocarburos, lluvia ácida, bioxido de azufre, oxido de nitrógeno, ozono, monóxido de carbono - Metales: metales carcinogénicos, arsénico, cadmio, cromo, manganeso, mercurio - Plaguicidas - Toxicología