Conclusions of the French Food Safety Agency on the toxicity of bisphenol A

Since more than 10 years, risk assessment of bisphenol A (BPA) is debated at the international level. In 2008, the U.S. National Toxicology Program (NTP) expressed some concern for adverse effects, at current level of exposure to BPA, on developmental toxicity. In this context, the French Food Safety Agency (AFSSA) decided to review the toxicity data on BPA with a special focus on this endpoint at doses below 5mg/kg bw/day (the no observed adverse effect level set by different regulatory bodies). This paper summarizes the conclusions of a collective assessment conducted by an expert Working Group from AFSSA. Studies were classified into 3 groups: (i) finding no toxicity, (ii) reporting results not considered to be of concern and (iii) indicating warning signals. The term "warning signal" means that no formal conclusion can be drawn regarding the establishment of a health based guidance value but the study raises some questions about the toxicity of BPA at low doses. It was concluded that studies are needed to ascertain the significance for human health of these warning signals and to be able to propose new methodologies for assessing the risks associated with low doses of BPA and more generally of endocrine disruptors

Contabilidad por la responsabilidad y precios de transferencia. Su aplicación en el perfeccionamiento empresarial cubano

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Adverse effects of endocrine disruptors on the foetal testis development: focus on the phthalates.

There are great concerns about the increasing incidence of abnormalities in male reproductive function. Human sperm counts have markedly dropped and the rate of testicular cancer has clearly augmented over the past four decades. Moreover, the prevalence rates of cryptorchidism and hypospadias are also probably increasing. It has been hypothesized that all these adverse trends in male reproduction result from abnormalities in the development of the testis during foetal and neonatal life. Furthermore, many recent epidemiological, clinical and experimental data suggest that these male reproductive disorders could be due to the effects of xenobiotics termed endocrine disruptors, which are becoming more and more concentrated and prevalent in our environment. Among these endocrine disruptors, we chose to focus this review on the phthalates for different reasons: 1) they are widespread in the environment; 2) their concentrations in many human biological fluids have been measured; 3) the experimental data using rodent models suggesting a reprotoxicity are numerous and are the most convincing; 4) their deleterious effects on the in vivo and in vitro development and function of the rat foetal testis have been largely studied; 5) some epidemiological data in humans suggest a reprotoxic effect at environmental concentrations at least during neonatal life. However, the direct effects of phthalates on human foetal testis have never been explored. Thus, as we did for the rat in the 1990s, we recently developed and validated an organ culture system which allows maintenance of the development of the different cell types of human foetal testis. In this system, addition of 10-4 M MEHP (mono-2-ethylhexyl phthalate), the most produced phthalate, had no effect on basal or LH-stimulated production of testosterone, but it reduced the number of germ cells by increasing their apoptosis, without modification of their proliferation. This is the first experimental demonstration that phthalates alter the development of the foetal testis in humans. Using our organotypic culture system, we and others are currently investigating the effect of MEHP in the mouse and the rat, and it will be interesting to compare the results between these species to analyse the relevance of toxicological tests based on rodent models

Ontogenesis of testicular function in humans.

The two major functions of the testis, steroidogenesis and gametogenesis, take place during fetal life. These two functions have been extensively studied in rodents and adult humans. However, their onset during fetal life is poorly documented in humans. In the first part of this work we presented both our experimental data and some data of literature concerning the development of the human fetal testis. In the second part of this article, using the organ culture system we previously developed, we have investigated the regulations or perturbations of fetal testis development both in rodent and human models. Our findings provide important insight into the potential role of exposure to environmental pollutants (physical factors, in particular ionizing radiation, cadmium and endocrine disruptors such as phthalates) during fetal testicular development and their potential deleterious effects on male fertility in adulthood. Our results highlight the specificity of the human model compared with rodent models

Pathology affecting Crocodylus acutus (Cuvier, 1807) in the Sabanalamar hatchery, Cuba

Poor management and feeding practices involved in rearing in captivity the American crocodile, Crocodylus acutus (Cuvier, 1807), are stressors that predispose to disease. In the crocodile culture operation at Sabanalamar, Pinar del Río Province, weakened physical condition and diseases have caused mortality in the young animals. This served as motivation for undertaking diagnoses to identify the pathologies that affect the juvenile stages of the crocodile under one system in captivity, and to evaluate the sensitivity of the pathogens detected to ten types of antibiotics. Ten juveniles of C. acutus were subjected to clinical, bacteriological, and histopathological examination. The pathogenic bacteria isolated in highest percentage belonged to the genera Aeromonas and Pseudomonas. Of these, Aeromonas were susceptible to amikacin and gentamicin, while Pseudomonas was resistant to all 10 antibiotics tested. The pathological alterations observed led to diagnosis of hypovitaminosis A, leading to weakened animals and the bacterial septicemia and mortality observed in juvenile stages.The management and poor feeding during breeding American crocodile Crocodylus acutus (Cuvier, 1807) are stressors that predispose to disease. In the breeding of C. acutus Sabanalamar, province of Pinar del Rio, Cuba, the weakening of the physical conditions and the onset of disease mortality occurred in juveniles of this species. That determine the need for first in Cuba a diagnosis of pathologies affecting this category low housing systems. Studied 10 juvenile C. acutus by bacteriological and histopathological examinations. Bacterial pathogens isolated in highest percent belong to the genera Aeromonas and Pseudomonas. Aeromonas was sensitive to antibiotics and gentamicin amikacin, whereas Pseudomonas present in all organ samples was resistant to 10 antibiotics tested. The pathological changes observed allowed diagnose malnutrition with vitaminosis process that led to a weakening of the animals and the emergence of bacterial septicemia cause mortality in juvenile American crocodile Sabanalamar Hatchery

Epigenetic control of nuclear architecture

The cell nucleus is a highly structured compartment where nuclear components are thought to localize in non-random positions. Correct positioning of large chromatin domains may have a direct impact on the localization of other nuclear components, and can therefore influence the global functionality of the nuclear compartment. DNA methylation of cytosine residues in CpG dinucleotides is a prominent epigenetic modification of the chromatin fiber. DNA methylation, in conjunction with the biochemical modification pattern of histone tails, is known to lock chromatin in a close and transcriptionally inactive conformation. The relationship between DNA methylation and large-scale organization of nuclear architecture, however, is poorly understood. Here we briefly summarize present concepts of nuclear architecture and current data supporting a link between DNA methylation and the maintenance of large-scale nuclear organization

MODIFICATION DE LA RADIOSENSIBILITE DES GONOCYTES DU RAT NOUVEAU-NE PENDANT LA PERIODE QUIESCENTE

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