Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Prevalencia y causas de ceguera en Perú: encuesta nacional / National survey on the prevalence and causes of blindness in Peru

OBJETIVO: Estimar la prevalencia de ceguera y deficiencia visual en adultos de Perú y precisar sus causas, evaluar la cobertura y la calidad de los servicios de cirugía de catarata y determinar las barreras que impiden acceder a esos servicios. MÉTODOS: Estudio poblacional transversal con muestreo aleatorio por conglomerado en dos pasos de personas de 50 años o más, representativo de todo el país, mediante la metodología estándar de la Evaluación Rápida de Ceguera Evitable. Se midió la agudeza visual y se examinó el cristalino y el polo posterior por oftalmoscopía directa. Se calculó la cobertura de cirugía de catarata y se evaluó su calidad, además de las causas de tener una agudeza visual < 20/60 y las barreras para acceder a ese tratamiento. RESULTADOS:Se examinaron 4 849 personas. La prevalencia de ceguera fue 2,0% (intervalo de confianza de 95%: 1,5-2,5%). La catarata fue la causa principal de ceguera (58,0%), seguida por el glaucoma (13,7%) y la degeneración macular relacionada con la edad (11,5%). Los errores de refracción no corregidos fueron la principal causa de deficiencia visual moderada (67,2%). La cobertura de cirugía de catarata fue de 66,9%, y 60,5% de los ojos operados de catarata logró una AV ≥ 20/60 con la corrección disponible. Las principales barreras para someterse a la cirugía de catarata fueron el alto costo (25,9%) y no saber que el tratamiento es posible (23,8%). CONCLUSIONES: La prevalencia de ceguera y deficiencia visual en Perú es similar a la de otros países latinoamericanos. La baja cobertura de cirugía de catarata y el envejecimiento poblacional indican que para aumentar el acceso a estos servicios se debe mejorar la educación de la población en salud ocular y la capacidad resolutiva de los servicios oftalmológicos y de cirugía de catarata, y reducir su costo.

OBJECTIVE: To estimate the prevalence of blindness and visual impairment among adults in Peru and to determine their causes, to evaluate the coverage and quality of the cataract surgical services and to investigate the barriers that inhibit access to these services. METHODS: A cross-sectional population study with two-stage random cluster sampling of individuals of ≥ 50 years old, representative of the entire country, using the standard methodology of the Rapid Assessment of Avoidable Blindness. Visual acuity was assessed and the condition of the lens and posterior pole examined by direct ophthalmoscopy. Cataract surgical coverage was calculated. Its quality, as well as the causes of visual acuity < 20/60 and the barriers to accessing surgical treatment were assessed. RESULTS: A total of 4 849 people were examined. Blindness prevalence was 2.0% (confidence interval of 95%: 1.5-2.5%). The main causes of blindness were cataract (58.0%), glaucoma (13.7%) and age-related macular degeneration (11.5%). Uncorrected refraction errors were the principal cause of moderate visual impairment (67.2%). Cataract surgical coverage was 66.9%. 60.5% of the eyes operated for cataracts achieved a visual acuity ≥ 20/60 with available correction. The main barriers to cataract surgery were the high cost (25.9%) and people being unaware that treatment was possible (23.8%). CONCLUSIONS: The prevalence of blindness and visual impairment in Peru is similar to that of other Latin American countries. Given the low cataract surgical coverage and the aging of the population, access to the services could be improved by increasing the population education on eye health and the response capacity of the ophthalmological and cataract surgical services, and by reducing the costs of the latter.

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.

La evidencia acerca de la controversia de las vacunas que contienen timerosal y su asociación con el autismo / Addressing the controversy regarding the association between thimerosal-containing vaccines and autism

La vacunación es una de las medidas de mayor impacto en la salud pública para la reducción de la morbimortalidad infantil. El timerosal es un compuesto orgánico del mercurio utilizado como preservante de los frascos multidosis. Eventualmente, en el Perú, surgen olas de controversia acerca de la seguridad de estas vacunas, asociándolas especialmente con el autismo. Como resultado de estas controversias, se han propuesto, incluso, leyes que prohíben este tipo de vacunas, lo que tendría un importante impacto en los costos y en los aspectos logísticos de la estrategia nacional de vacunación. En este artículo se revisa la literatura sobre las principales controversias acerca de las vacunas que contienen timerosal y su supuesta asociación con el autismo. Se realiza una aproximación histórica sobre estas controversias, se hace una actualización de la evidencia científica disponible al momento, y se revisa la posición de los organismos internacionales más importantes con respecto a este tema. Se concluye que la evidencia científica no apoya la noción que exista una asociación entre el uso del timerosal en las vacunas con los trastornos del espectro autista en niños.

Vaccination is one of the most important public health interventions in the reduction childhood morbidity and mortality. Thimerosal is an organic mercury compound used as preservante in multi-dose vials. Often in Peru, there are waves of controversy about the safety of this type of vaccines, mainly arguing that there is an association between them and autism. As a result of these controversies, there have been some voices asking for laws banning thimerosal-containing vaccines, which would have a large impact in costs and the logistic aspects of the public vaccination programs. The aim of this article is to review the literature for the main controversies about thimerosal in vaccines and its supposed association to autism. We made an historical review about these controversies given the available scientific evidence and the statements from important international organizations. We concluded that the current available evidence do not support an association between thimerosal and childhood neurodevelopmental disorders, such as autism.

Tratamientos biológicos del autismo y dietas de eliminación / Biological treatments of autism, elimination diets: a critical review

This paper presents some critical considerations regarding the growing adoption, by families, of alternative treatments and diets for the treatment of various disorders like autism in children. Research does not seem to support such practices, with the exception of the relationship between timesoral and vaccines, neurological and cardiac disorders. Issues to consider are pointed out in the need to opt for biological treatments, and the need for families and research teams to work together for the purpose of clarifying such procedures.

El objetivo de este trabajo es presentar consideraciones críticas en relación a la creciente adopción, por parte de las familias de niños con trastornos del desarrollo, de tratamientos alternativos y dietas para reducir los síntomas de diversas alteraciones tales como el autismo, SDAH y otros. Las investigaciones no parecen apoyar tales prácticas, a excepción de la creciente evidencia de la relación entre el timerosal de las vacunas y afecciones cardíacas y neurológicas. Se señalan los elementos a tener en cuenta para optar por los tratamientos biológicos y dietas, junto con insistir en la necesidad de mancomunar esfuerzos entre familias y equipos de investigación para desarrollar estudios que clarifiquen los efectos de tales procedimientos.

Comparative evaluation of phenol and thimerosal as preservatives for a candidate vaccine against American cutaneous leishmaniasis

For decades thimerosal has been used as a preservative in the candidate vaccine for cutaneous leishmaniasis, which was developed by Mayrink et al. The use of thimerosal in humans has been banned due to its mercury content. This study addresses the standardization of phenol as a new candidate vaccine preservative. We have found that the proteolytic activity was abolished when the test was conducted using the candidate vaccine added to merthiolate (MtVac) as well as to phenol (PhVac). The Montenegro's skin test conversion rates induced by MtVac and by PhVac was 68.06 percent and 85.9 percent, respectively, and these values were statistically significant (p < 0.05). The proliferative response of peripheral mononuclear blood cells shows that the stimulation index of mice immunized with both candidate vaccines was higher than the one in control animals (p < 0.05). The ability of the candidate vaccines to induce protection in C57BL/10 mice against a challenge with infective Leishmania amazonensis promastigotes was tested and the mice immunized with PhVac developed smaller lesions than the mice immunized with MtVac. Electrophoresis of phenol-preserved antigen revealed a number of proteins, which were better preserved in PhVac. These results do in fact encourage the use of phenol for preserving the immunogenic and biochemical properties of the candidate vaccine for cutaneous leishmaniasis.

Seguridad de las vacunas que contienen timerosal: Declaración del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología / Safety of thimerosal containing vaccines. Statement of the Consultive Committee of Immunizations on behalf of the Chilean Infectious Diseases Society

El timerosal es un derivado del mercurio utilizado desde 1930 como preservante de vacunas. En las últimas décadas ha sido cuestionada su seguridad, especialmente por la posibilidad de toxicidad neurológica. La revisión de varios estudios realizados en niños que recibieron vacunas que contienen timerosal y la posición de organismos de expertos internacionales en relación al uso de este compuesto en vacunas, permite al Comité Consultivo de Inmunizaciones concluir que no existe evidencia de eventos adversos en lactantes o niños por exposición al timerosal contenido en vacunas rutinarias y, por lo tanto, no habría razón para modificar las actuales prácticas de inmunización en Chile.

Thimerosal is a mercury derivative included in vaccines since 1930 with the aim to prevent microbial contamination. During the last decades, the use of thimerosal has been questioned, specifically because of a potential association with neurotoxicity. After a thorough review of published studies on pediatric use of thimerosal-containing vaccines, and of position papers from international expert groups, the Consultive Committee of Immunizations of the Chilean Society of Infectious Diseases concludes that there is no solid evidence of adverse events associated with the use of thimerosal containing vaccines in infants and children. Therefore, a change in current vaccine practices refererred to thimerosal-containing vaccines is not justified in Chile.

Thimerosal allergy and clinical relevance in Thailand.

BACKGROUND: Thimerosal or merthiolate is used as an antiseptic and a preservative in topical medicaments, cosmetics, and vaccines. Thimerosal is known to cause delayed type hypersensitivity. However, there is argument about the clinical relevance and risk of using thimerosal-preserved products in thimerosal allergic individuals. OBJECTIVE: Retrospective review of patch test results from the Ramathibodi Hospital patch test clinic to determine the prevalence and relevance of allergic reactions to thimerosal in Thailand. MATERIAL AND METHOD: During a 5-year period, thimerosal was patch tested in all patients tested for possible allergic contact dermatitis. Thimerosal was the second most common allergen causing a positive patch test reaction. RESULTS: Of the 433 patients tested, 46 (10.62%) were positive to thimerosal. However, despite the high prevalence of positive reactions none was clinically relevant to their present dermatitis, none of the patients reported reactions to vaccination or cross-reaction to piroxicam. CONCLUSION: There was a high rate of sensitization to thimerosal in Thai patients, but were of little clinical relevance. The author does not advise thimerosal allergic individuals to avoid vaccination, although the small risk of local dermatitis should be pointed out. The topical use of thimerosal containing antiseptics should be avoided.

Thimerosal toxicity and autism

Autism is a chronic problem that begins in the first three years of life, in which the child fails to develop his communication skills with the surrounding. The estimated number of autistics in Libya is 11263. One of the hypotheses concerning etiology of autism is mercury toxicity, which is available in a vaccine preservative called thimerosal

Skin reactions to thimerosal and Leishmania in dogs from a leishmaniasis endemic area: it is better to keep them apart

Positive Montenegro's skin test is a delayed type hypersensitivity reaction widely used as indicative of previous infection with Leishmania in both humans and dogs. Montenegro's antigen consists of a crude Leishmania antigen solution, usually containing thimerosal as preserving agent. In this work it is shown that a large proportion of dogs (11 out of 56) examined in an endemic area of leishmaniasis presented induration at the site of injection of a diluent containing thimerosal alone. This clearly demonstrates that thimerosal leads to a high number of false positive skin reactions in dogs and that its use in Montenegro's skin test antigenic preparations should be avoided