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.

Effects of chronic low-dose aflatoxin B1 exposure in lactating Florida dairy goats.

In the past few years there has been a growing trend in the prevalence of aflatoxins, attributable to climate change, in substances destined for animal feeding, together with an increase in dairy product consumption. These facts have triggered great concern in the scientific community over milk pollution by aflatoxin M1. Therefore, our study aimed to determine the transfer of aflatoxin B1 from the diet into milk as AFM1 in goats exposed to different concentrations of AFB1, and its possible effect on the production and serological parameters of this species. For this purpose, 18 goats in late lactation were divided into 3 groups (n = 6) and exposed to different daily doses of aflatoxin B1 (T1 = 120 µg; T2 = 60 µg, and control = 0 µg), during 31 d. Pure aflatoxin B1 was administered 6 h before each milking in an artificially contaminated pellet. The milk samples were taken individually in sequential samples. Milk yield and feed intake were recorded daily, and a blood sample was extracted on the last day of exposure. No aflatoxin M1 was detected, either in the samples taken before the first administration, or in the control group ones. The aflatoxin M1 concentration detected in the milk (T1 = 0.075 µg/kg; T2 = 0.035 µg/kg) increased significantly on a par with the amount of aflatoxin B1 ingested. The amount of aflatoxin B1 ingested did not have any influence on aflatoxin M1 carryover (T1 = 0.066% and T2 = 0.060%), these being considerably lower than those described in dairy goats. Thus, we concluded that the concentration of aflatoxin M1 in milk follows a linear relationship with respect to the aflatoxin B1 ingested, and that the aflatoxin M1 carryover was not affected by the administration of different aflatoxin B1 doses. Similarly, no significant changes in the production parameters after chronic exposure to aflatoxin B1 were observed, revealing a certain resistance of the goat to the possible effects of that aflatoxin.

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.

Premenstrual and menstrual changes reported after COVID-19 vaccination: The EVA project.

BACKGROUND: Menstrual disorders were not reported as a possible secondary effect in any of the clinical trials for the SARS-CoV-2 vaccines. AIM: To describe the prevalence of perceived premenstrual and menstrual changes after COVID-19 vaccine administration. DESIGN: Cross-sectional study. METHODS: A total of 14,153 women (mean age 31.5 ± 9.3 years old) who had received the full course of vaccination at least three months earlier were included in this cross-sectional study. Data including the type of vaccine administered, perceived changes in the amount and duration of menstrual bleeding, presence of clots, cycle length, and premenstrual symptoms were collected through a retrospective online survey from June to September 2021. RESULTS: Of the women who participated in this study, 3136 reported no menstrual changes and 11,017 (78% of the study sample) reported experiencing menstrual cycle changes after vaccination. In summary, women who reported menstrual changes after vaccination were older (overall p < 0.001) and slightly more smokers (p = 0.05) than women who did not report any changes. The most prevalent changes in relation to premenstrual symptoms were increased fatigue (43%), abdominal bloating (37%), irritability (29%), sadness (28%), and headaches (28%). The most predominant menstrual changes were more menstrual bleeding (43%), more menstrual pain (41%), delayed menstruation (38%), fewer days of menstrual bleeding (34.5%), and shorter cycle length (32%). CONCLUSION: Women vaccinated against COVID-19 usually perceive mild menstrual and premenstrual changes. Future studies are warranted to clarify the physiological mechanisms behind these widely reported changes.

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.

Evaluation of the Toxicity of Bisphenol A in Reproduction and Its Effect on Fertility and Embryonic Development in the Zebrafish (Danio rerio).

Bisphenol A (BPA) is a chemical substance commonly used in the manufacture of plastic products. Its inhalation or ingestion from particles in suspension, water, and/or polluted foods can trigger toxic effects related to endocrine disruption, resulting in hormonal, reproduction, and immunological alterations in humans and animals. The zebrafish (Danio rerio) is an ideal experimental model frequently used in toxicity studies. In order to assess the toxic effects of BPA on reproduction and embryonic development in one generation after parental exposure to it, a total of 80 zebrafish, males and females, divided into four groups in duplicate (n = 20) were exposed to BPA concentrations of 500, 50, and 5 µg L-1, along with a control group. The fish were kept in reproduction aquariums for 21 days. The embryos obtained in the crosses were incubated in a BPA-free medium and observed for signs of embryotoxicity. A histopathological study (under optical and electron microscopes) was performed of adult fish gonads. The embryos of reproducers exposed to BPA were those most frequently presenting signs of embryotoxicity, such as mortality and cardiac and musculoskeletal malformations. In the histopathological studies of adult individuals, alterations were found in ovocyte maturation and in spermatazoid formation in the groups exposed to the chemical. Those alterations were directly related to BPA action, affecting fertility in both sexes, as well as the viability of their offspring, proportionally to the BPA levels to which they were exposed, so that our results provide more information by associating toxic effects on the offspring and on the next generation.

Tremorgenic mycotoxicosis in cattle, caused by Claviceps paspali.

Claviceps paspali is a fungus that mainly parasitises Paspalum dilatatum, generating a structure denominated sclerotium, in which indole-diterpenoid alkaloids are isolated. Its action mechanism is related to the inhibition of the gamma-aminobutyric acid receptor. It basically affects bovines, triggering the tremorgenic syndrome, the prevalence of this intoxication being relatively low in Europe. This work describes a clinical case on a cattle farm in Seville (southern Spain), composed of 91 bovines, 60% of which were principally affected with nervous clinical signs. The diagnosis was based on a clinical inspection of the animals, as well as of the presence of paspalum seed heads containing the sclerotia of Claviceps paspali in the plants present in the pastures. The causal agent was identified as being Claviceps paspali, which had parasitised numerous examples of Paspalum paspaloides. The indole-diterpenoid alkaloids produced by Claviceps paspali were identified using ultraviolet-visible spectrophotometry and mass spectrometry. At present, no effective aetiological treatment has been described for poisoning caused by this mycotoxin, so a supportive treatment was administered, and different handling methods were applied, resulting in the complete recovery of the animals. Finally, it was concluded that unusually high humidity and temperature levels for the region triggered the development of the sclerotium generated by this fungus.

Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against Staphylococcus aureus Isolated from Caprine Clinical Mastitis.

Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on S. aureus isolated from mastitis goats' milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller-Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 105 and 108 CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC50 values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC24/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60-180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating S. aureus in lactating goats.

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.