An Overview of the Health Effects of Bisphenol A from a One Health Perspective.

Bisphenol A (BPA) is a chemical compound, considered as an "emerging pollutant", that appears ubiquitously, contaminating the environment and food. It is an endocrine disruptor, found in a multitude of consumer products, as it is a constituent of polycarbonate used in the manufacture of plastics and epoxy resins. Many studies have evaluated the effects of BPA, using a wide range of doses and animal models. In this work, we carried out a review of relevant research related to the effects of BPA on health, through studies performed at different doses, in different animal models, and in human monitoring studies. Numerous effects of BPA on health have been described; in different animal species, it has been reported that it interferes with fertility in both females and males and causes alterations in their offspring, as well as being associated with an increase in hormone-dependent pathologies. Similarly, exposure to BPA has been related to other diseases of great relevance in public health such as obesity, hypertension, diabetes, or neurodevelopmental disorders. Its ubiquity and nonmonotonic behavior, triggering effects at exposure levels considered "safe", make it especially relevant when both animal and human populations are constantly and inadvertently exposed to this compound. Its effects at low exposure levels make it essential to establish safe exposure levels, and research into the effects of BPA must continue and be focused from a "One Health" perspective to take into account all the factors that could intervene in the development of a disease in any exposed organism.

Comparative study of tricaine methanesulfonate (MS-222) and eugenol as euthanasia agents in zebrafish (Danio rerio) as an experimental model.

In experimental procedures inevitably leading to the sacrifice of animals, suitable measures should be taken to minimise their pain and suffering as much as possible, as well as to prevent any modification or masking in the experimental results obtained. An overdose of anaesthetic is the method of euthanasia most employed in fish, since it is effective and easy to apply. Our objectives were to compare the efficacy of eugenol and of tricaine methanesulfonate (MS-222) as euthanasia agents in zebrafish, and to make a histological evaluation of the possible effects derived from their application. The concentrations established for eugenol were 0.25 and 0.35 mg/mL, and those for MS-222 were 0.25 and 0.50 mg/mL, for both the buffered solution and the non-buffered one. Eugenol turned out to be a stronger euthanasia agent than MS-222 in zebrafish, presenting with significantly shorter euthanasia times. However, the exposure of the fish to euthanasia doses of eugenol triggered branchial alterations, in addition to serious lesions and changes in their nerve tissue. The results obtained with MS-222 also revealed a marked branchial alteration derived from its use. In this respect, the addition of a buffer to the MS-222 solution enhanced the effectiveness of the drug, with significantly shorter euthanasia times being achieved than with the non-buffered solution, and diminished the severity of the lesions described. We therefore determined that the buffered MS-222 solution is the most effective, reliable and safest method of euthanasia for use in research on zebrafish.

Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice.

Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.

Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice.

Bisphenol A (BPA) is considered as being an emerging pollutant, to which both animal and human populations are continuously and inadvertently exposed. The identification of indirect biomarkers of effect could be a key factor in determining early adverse outcomes from exposure to low doses of BPA. Thus, this study on mice aims to evaluate and identify indirect biomarkers of effect through the analysis of their blood biochemistry, and of certain reproduction parameters after exposure to different BPA concentrations (0.5, 2, 4, 50, and 100 µg/kg BW/day) in drinking water over generations. Our results showed that there were no modifications in the reproductive parameters evaluated, like estrous cycle duration, litter size, or the percentage of the young alive at reaching the weaning stage, at the exposure levels evaluated. However, there were modifications in the biochemical parameters, e.g., alterations in the glucose levels, that increased significantly (p < 0.05) in the breeders at the higher exposure doses (50 and 100 µg/kg BW/day in F1; 50 µg/kg BW/day in F2 and 100 µg/kg BW/day in F3), that would suggest that the BPA could induce hyperglycemia and its complications in adult animals, probably due to some damage in the pancreas cells; albumin, that increased in the breeders exposed to the highest dose in F1 and F3, inferring possible hepatic alterations. Further, total proteins showed a diminution in their values in F1 and F2, except the group exposed to 100 µg/kg BW/day, whereas in F3 the values of this parameter increased with respect to the control group, this aspect likely being related to a possible hepatic and renal alteration. Based on these results, glucose, albumin, and total proteins could initially be considered as early indicators of indirect effect after prolonged exposure to low BPA doses over generations.

Preneoplastic and neoplastic changes in the Leydig cells population in mice exposed to low doses of cadmium.

The morphological consequences of chronic exposition to low doses of cadmium (Cd) in the Leydig cells population were investigated in 40 sexually mature male mice at morphological and ultrastructural levels. Animals were orally exposed to cadmium (0.015 g/L of CdCl(2) in drinking water) for 3, 6, 12 and 18 months and then sacrificed, samples were collected for toxicological, light and electron microscope studies. Vascular lesions were evident from 6 months of Cd exposure, the severity of the morphological changes observed in the testicular vases were highly and clearly correlated to the time of exposure to Cd. The severity of the Leydig cells morphological changes were increasing along the time of exposure. Presence of cytoplasm vacuolization and degenerative images of the cells were frequent after 12 months of Cd exposure. Also two Leydig cells tumours after 12 and 18 months Cd exposure were presented. These results indicate that prolonged exposures to low doses of Cd are able to induce morphological damage on the Leydig cells.