Timerosal en las vacunas: ¿blanco, negro, o más bien todo lo contrario? / Thimerosal in vaccines: white, black, or quite the opposite?

El presente artículo tiene por objetivo analizar la controversia ocurrida en Chile, especialmente durante los últimos meses, en relación a un proyecto de ley que busca prohibir la fabricación, importación, comercialización o distribución de vacunas que contengan dentro de sus compuestos, en cualquier nivel de concentración, timerosal o compuestos organomercúricos. Sin constituir una síntesis formal de toda la investigación existente, se analiza la evidencia científica que los distintos actores han utilizado, las razones de la controversia y las anomalías en el proceso de toma de decisión sanitaria.

This article analyzes the recent controversy regarding the introduction of a bill to Chilean Congress that aims to ban thiomersal and/or any trace of organomercurial compounds from vaccines in the country. Rather than providing a formal overview of all available evidence, this analysis focuses on the reasons behind the controversy, the scientific evidence invoked by both sides in the debate, and the anomalies in the healthcare decision-making process.

Prenatal exposure to organomercury, thimerosal, persistently impairs the serotonergic and dopaminergic systems in the rat brain: implications for association with developmental disorders.

Thimerosal, an organomercury compound, has been widely used as a preservative. Therefore, concerns have been raised about its neurotoxicity. We recently demonstrated perturbation of early serotonergic development by prenatal exposure to thimerosal (Ida-Eto et al. (2011) [11]). Here, we investigated whether prenatal thimerosal exposure causes persistent impairment after birth. Analysis on postnatal day 50 showed significant increase in hippocampal serotonin following thimerosal administration on embryonic day 9. Furthermore, not only serotonin, striatal dopamine was significantly increased. These results indicate that embryonic exposure to thimerosal produces lasting impairment of brain monoaminergic system, and thus every effort should be made to avoid the use of thimerosal.

Neurotoxicity of organomercurial compounds.

Mercury is a ubiquitous contaminant, and a range of chemical species is generated by human activity and natural environmental change. Elemental mercury and its inorganic and organic compounds have different toxic properties, but all them are considered hazardous in human exposure. In an equimolecular exposure basis, organomercurials with a short aliphatic chain are the most harmful compounds and they may cause irreversible damage to the nervous system. Methylmercury (CH(3)Hg(+)) is the most studied following the neurotoxic outbreaks identified as Minamata disease and the Iraq poisoning. The first description of the CNS pathology dates from 1954. Since then, the clinical neurology, the neuropathology and the mechanisms of neurotoxicity of organomercurials have been widely studied. The high thiol reactivity of CH(3)Hg(+), as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH(3)Hg(+) for specific cell types and brain structures, which is not yet fully understood. The main mechanisms involved are inhibition of protein synthesis, microtubule disruption, increase of intracellular Ca(2+) with disturbance of neurotransmitter function, oxidative stress and triggering of excitotoxicity mechanisms. The effects are more damaging during CNS development, leading to alterations of the structure and functionality of the nervous system. The major source of CH(3)Hg(+) exposure is the consumption of fish and, therefore, its intake is practically unavoidable. The present concern is on the study of the effects of low level exposure to CH(3)Hg(+) on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 micro g/kg body weight/day by the WHO and US FDA and, recently, 0.1 micro g/kg body weight/day by the US EPA. Unfortunately, these levels are easily attained with few meals of fish per week, depending on the source of the fish and its position in the food chain.

Technical report: mercury in the environment: implications for pediatricians.

Mercury is a ubiquitous environmental toxin that causes a wide range of adverse health effects in humans. Three forms of mercury (elemental, inorganic, and organic) exist, and each has its own profile of toxicity. Exposure to mercury typically occurs by inhalation or ingestion. Readily absorbed after its inhalation, mercury can be an indoor air pollutant, for example, after spills of elemental mercury in the home; however, industry emissions with resulting ambient air pollution remain the most important source of inhaled mercury. Because fresh-water and ocean fish may contain large amounts of mercury, children and pregnant women can have significant exposure if they consume excessive amounts of fish. The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health. This review provides pediatricians with current information on mercury, including environmental sources, toxicity, and treatment and prevention of mercury exposure.

Epidemics of vascular toxicity and pulmonary hypertension: what can be learned?

Epidemics of vascular disease caused by toxins and infectious agents affecting both humans and animals have been common in history. Examples of agents implicated include anorexients, ergotamine, mercury, arsenic, vinyl chloride, thorotrast, plant alkaloids, nitrites, toxic oil, tryptophan and bacterial, viral and parasitic infections. A major characteristic of these disorders is endothelial dysfunction, which may manifest itself in vasospastic disorders, sclerodermiform skin lesions, fibrosis, osteolytic lesions, polyneuropathy and portal and pulmonary hypertension. Angiosarcoma may also be a late outcome. These diseases are more common than is generally appreciated. The aetiology is usually multifactorial. This and other factors contribute to delayed recognition.

[Assessment of autonomic neurotoxicity of environmental and occupational factors as determined by heart rate variability: recent findings].

The measurement of heart rate variability (coefficient of variation of ECG R-R intervals) provides a promising approach for the objective assessment of the autonomic nervous function. It is noninvasive and clinically practical, although it tends to be distorted by confounding factors such as age, tobacco and alcohol. In particular, two components of the respiratory sinus arrhythmia with a high frequency (HF) of 0.15-0.4 Hz and Mayer wave related sinus arrhythmia with a low frequency (LF) of 0.04-0.15 Hz in the heart rate variability, which were computed by autoregressive spectral and component wave analyses, reflect parasympathetic and sympathetic activities, respectively. This article is intended to present an overview of research, utilizing this frequency domain method, in environmental and occupational health. The available literature, addressing the impact of some chemicals and work-related factors on the human autonomic nervous system, indicates that parasympathetic activity appears to be more vulnerable to these factors than does sympathetic activity. Since decreased cardiac vagal tone is associated with an increased risk of sudden cardiac death or coronary heart disease, attention should be directed to further discovery of hazardous factors in the environment and workplace, which may pose potential autonomic neurotoxic risks.

Thimerosal positivities: the rôle of SH groups and divalent ions.

For a better understanding of the mechanistic details of the interactions of organomercury compounds inside the skin, 32 subjects who previously had given positive patch-test reactions to thimerosal (TH) and negative reactions to thiosalicylic acid, were divided into 2 groups. 16 subjects were repatch tested to ethylmercury chloride (EtHgCl) and to solutions containing EtHgCl mixed with L-cysteine and glutathione, respectively. The remaining 16 were repatch tested to EtHgCl and to solutions containing EtHgCl mixed with chlorides of Zn, Mg, and Mn, respectively. The results showed that whilst L-cysteine, glutathione and ZnCl2 were able to abolish or to reduce the positive reactions to EtHgCl, chlorides of Mg and Mn were unable to do so. Patch tests revealed that in causing positive reactions to TH, EtHg probably interacted with thiol groups and with Zn ions, as in biological systems when causing toxic effects. The limited number of TH reactions in the general population, the constant presence of concomitant positive reactions to EtHgCl and MeHgCl, and the lack of cross-reactivity with other organic or inorganic mercury compounds, lead us to speculate that reactions to TH are due to organomercury alkyl compounds, and that positive subjects have a constitutively reduced capability to metabolize organomercury compounds, rather than to reveal previous exposure.

Thimerosal positivities: the role of organomercury alkyl compounds.

Contact allergy to thimerosal (TH) has not been considered a marker for mercury allergy, since there is a low degree of cross-sensitivity to inorganic as well as to organic mercury salts. 40 subjects, who previously gave a positive patch test reaction only to thimerosal 0.1% pet. (Hermal), when simultaneously repatch-tested to solutions containing TH, mersalyl acid, p-amino-phenylmercuric acid, mercuric acetate and thiosalicylic acid, respectively, gave positive reactions only to TH. 36 out of 40 subjects were divided into 2 groups of 18 subjects and simultaneously repatch-tested to solutions containing TH, methylmercury chloride (MeHgCl), thiosalicylic acid, and, ethylmercury chloride (EtHgCl), respectively. EtHgCl was tested in the 1st group at 0.031% and in the 2nd group at 0.015%. The results showed that all subjects gave concomitant positive reactions to TH, EtHgCl and MeHgCl. EtHgCl 0.031% gave a higher number of reactions than EtHgCl 0.015%, underlining the rôle of the solvent in these reactions. Patch test results in 300 consecutive patients to a standard series, to which MeHgCl was added, showed that MeHgCl and TH were never able to give isolated positive reactions, and that the concomitant positive reactions occurred in only 3.6% of subjects. In conclusion, our data seem to suggest that the positive reactions to TH found in our patients were due to EtHgCl, and that the structural similarities with MeHgCl were so close that the skin reacted against each as if they were identical.

Mercury as a potential hazard for the dental practitioner.

Mercury has been used for centuries for medical, chemical, metallurgical and electrical applications. It is an element of mystery, which in its metallic form is an enticing silvery liquid that can be as fascinating as it is dangerous. Its use in dental amalgam has a potential for continuous occupational exposure of dental practitioners to mercury vapor. It is imperative that the dental practitioner understands the hazards associated with the use of mercury, and controls exposures to prevent the development of any untoward effects. This article provides an overview of the toxicology of the different forms of mercury to which human exposure occurs and addresses safety issues associated with mercury vapor, the primary form of mercury encountered in the practice of dentistry.

Influencia de los diuréticos en el resultado de los análisis clínicos / Influence of diuretics on the result of clinical analysis

En este trabajo se realizó una revisión de los principales grupos de diuréticos, sus sitios y mecanismos de acción y sus efectos sobre las pruebas de laboratorio. Se analizó el efecto de los diuréticos sobre: el estado ácido base, los electrolitos séricos y urinarios, el ácido úrico sérico y urinario y sobre la glucemia. También se describió la influencia de los diuréticos sobre los análisis de orina. Finalmente, los efectos hematológicos de los mismos. El objetivo de este trabajo fue estudiar la influencia de los diuréticos en los análisis clínicos, buscando los mecanismos fisiopatológicos o metodológicos de los casos citados

Influencia de los diuréticos en el resultado de los análisis clínicos / Influence of diuretics on the result of clinical analysis

En este trabajo se realizó una revisión de los principales grupos de diuréticos, sus sitios y mecanismos de acción y sus efectos sobre las pruebas de laboratorio. Se analizó el efecto de los diuréticos sobre: el estado ácido base, los electrolitos séricos y urinarios, el ácido úrico sérico y urinario y sobre la glucemia. También se describió la influencia de los diuréticos sobre los análisis de orina. Finalmente, los efectos hematológicos de los mismos. El objetivo de este trabajo fue estudiar la influencia de los diuréticos en los análisis clínicos, buscando los mecanismos fisiopatológicos o metodológicos de los casos citados (AU)

Carcinogenicity of mercury and mercury compounds.

Mercury and mercury compounds are widely used in modern society, but only sparse data are available on their carcinogenicity. Methylmercury chloride causes kidney tumors in male mice. Mercury chloride has shown some carcinogenic activity in male rats, but the evidence for female rats and male mice is equivocal. Other mercury compounds and metallic mercury have not been tested adequately in experimental animals. Epidemiologic data are available for chloralkali workers, dentists and dental nurses, and nuclear weapons workers, three groups occupationally exposed to low levels of mercury and its compounds, but those highly exposed in the past, such as miners, or populations which have suffered massive environmental exposure have not been adequately studied. However, the sparse epidemiologic data point toward the possibility of a risk of lung, kidney, and central nervous system tumors. Better data are needed on the carcinogenicity of mercury and mercury compounds in humans and experimental animals.

[Fertility of workers exposed to herbicides and pesticides]. / Fertilität bei Exponierten gegenüber Pflanzenschutz- und Schädlingsbekämpfungsmitteln.

Twenty-one workmen exposed to herbicide as organic mercury compounds and to pesticide as halogenic hydrocarbon has been investigated concerning their fertility. If the concentrations of organic mercury compounds increase in the air of the place of employment then the levels of this heavy metal are also higher in the urine and in the ejaculate, and the fertility is reduced. It could also be established that a correlation exists between the concentration of pesticide in the place of employment and the male fertility, especially in cases with an excess of maximum permitted concentrations.

[Mercury--is it a respiratory tract allergen?]. / Le mercure est-il un allergène des voies respiratoires.

Mercury is a well-known allergen in dermato-allergology, often manifesting as delayed type hypersensitivity contact eczema. Immediate hypersensitivity reactions (urticaria, anaphylactic shock) have also been described for this allergen, most frequently seen in patients with the delayed type contact eczema. To our knowledge this allergen has not been implicated in production of respiratory symptoms. We describe a patient who had aggravation of asthma by mercury contained in dental amalgam. When the dental amalgam was removed there was a great improvement in his asthma. This observation suggests that mercury in the form of dental amalgam may also be an allergen of the respiratory tract, which should not be surprising, bearing in mind the work that shows the existence of mercury vapours from dental amalgam.

[Toxic glomerulonephritis]. / Les néphropathies glomérulaires d'origine toxique.

Most glomerulopathies are immunologically-mediated. Their pathogenesis is now better understood. The role of cell-mediated immunity has recently been envisaged. The role of circulating antibodies now seems to be more important than that of circulating immune complexes. Antibodies may recognize structural or "planted" antigens in the kidney, the latter being non-renal molecules that may bind renal structures for non-immune reasons. The linear or granular pattern observed at immunofluorescence depends upon the regular or irregular distribution of the antigen. In susceptible individuals, various toxins (heavy metals such as mercury or gold, drugs with an SH group, non-steroidal anti-inflammatory agents) may induce an immune glomerulopathy. It has recently been shown that Brown-Norway rats exposed to one of the above-mentioned agents develop anti-self class II T lymphocytes that are responsible for a polyclonal activation of B cells. Among the various autoantibodies that are produced, some have a nephritogenic potential. Other drugs are responsible for glomerular lesions due to a direct toxic effect of the compound. Doxorubicin induces a nephrotic syndrome in the rabbit, while mitomycin induces a haemolytic uraemic syndrome in humans. Finally, drug addiction often leads to glomerulosclerosis.

Effect of organic and inorganic mercury compounds on the growth of incisor and tibia in rats.

The pharmacological effects of methyl mercury chloride (MMC) and mercuric chloride (HgCl2) (2-16 mg/Kg per day subcutaneously, for 6 d) upon the growth were studied in the incisors and proximal tibiae of immature rats histologically. Lead acetate was used as a time marker. 1. Mercury compounds slightly affected the body weight gains of the rats but apparently inhibited the longitudinal growth of proximal tibia and the effect increased with higher dosages. 2. Mercury compounds definitely inhibited not only the longitudinal growth (incisor growth) but also the appositional growth (dentin formation) of incisal dentin. 3. The inhibitory effect on the growth was ranked as follows: bone growth greater than dentin formation greater than incisor growth. 4. The actions of MMC on the growth of incisors and proximal tibiae appeared gradually and the response was biphasic; stimulatory and then inhibitory. The inhibitory effect appeared even after the injection was discontinued and appeared more extremely than during the injections. 5. In HgCl2 groups the inhibitory effect on the growth appeared rapidly. The effect increased with higher dosages and became stronger as the injections were repeated. However, this effect was weakened promptly after the injection was discontinued. 6. The repeated injections of mercury compounds hardly affected the level of serum calcium but disturbed the calcification of incisal dentin. From the above-mentioned results a possible mechanism was discussed. It is suggestive that MMC acts directly upon a cell and is transported into it. Once MMC was introduced into a cell it is slowly demethylated to inorganic Hg and acts as the demethylated mercury. When accumulated mercury is slight in volume, it stimulates and then inhibits the cell function with increasing mercury. However HgCl2 binds directly with an effector cell membrane in loose fashion. This may cause the ready reversibility of the effect.