Characteristics and treatment of Brazilian pulp and paper mill effluents: a review.

Pulp and paper industries are very important for developing the Brazilian economy. During production processes, many effluents are generated with high polluting potential. The objective of this study is to conduct an extensive literature review on the characteristics of effluents and treatment forms adopted by Brazilian mills in this industrial sector. Most consulted studies address raw (without treatment) and secondary (after biological treatment) effluents, considering their main characteristics like pH, chemical and biochemical oxygen demands (COD and BOD, respectively), color, solids, organochlorines, toxicity, estrogenic activity, and phenols. Raw effluents differ considerably in composition, depending on the type of paper produced, the pulping process employed, and other steps, like pulp bleaching. Raw effluent characteristics indicate that this effluent cannot be directly disposed of into water bodies, because it does not comply with federal and state disposal standards. Secondary effluents normally comply with Brazilian legislations, although some studies have reported COD and total phenol concentrations higher than disposal standards, suggesting that additional treatments are necessary. Treated effluent reuse was verified in some Brazilian mills, while its disposal in eucalyptus plantations has been considered a promising alternative for irrigation purposes.

Lethal and long-term effects of landfill leachate on Eisenia andrei earthworms: Behavior, reproduction and risk assessment.

Leachate is difficult to biodegrade, and presents variable physical, chemical and biological characteristics, as well as high toxicological potential for soil, groundwater and water bodies. In this context, untreated leachate toxicity was evaluated through acute and chronic exposures in Eisenia andrei earthworms. Physico-chemical leachate characterizations indicate a complex composition, with high organic matter (COD - 10,634 mg L-1) and ammoniacal nitrogen (2388 mg L-1) concentrations. Metals with carcinogenic potential, such as Cr, As and Pb, were present at 0.60, 0.14 and 0.01 µg L-1, respectively and endocrine disrupting compounds were detected in estradiol equivalents of 660 ± 50 ng L-1. Acute tests with Eisenia andrei indicated an LC50 (72 h) of 1.3 ± 0.1 µL cm-2 in a filter paper contact test and 53.9 ± 1.3 mL kg-1 in natural soil (14 days). The EC50 in a behavioral test was estimated as 31.6 ± 6.8 mL kg-1, indicating an escape effect for concentrations ranging from 35.0 to 70.0 mL kg-1 and habitat loss from 87.5 mL kg-1 of leachate exposure. Chronic exposure (56 days) led to reproduction effects, resulting in a 4-fold decreased cocoon production and 7-fold juvenile decrease. This effect was mainly attributed to the possible presence of endocrine disrupting compounds. An estimated NOAEL of 1.7 mL L-1 and LOAEL of 3.5 mL L-1 were estimated for earthworms exposed to the assessed effluent. Extremely high-risk quotients (RQ ≥ 1) were estimated based on leachate application in irrigation. Thus, adequate municipal solid waste management is paramount, especially with regard to generated by-products, which can result in high toxicological risks for terrestrial organisms.

Biodegradation of natural and synthetic endocrine-disrupting chemicals by aerobic granular sludge reactor: Evaluating estrogenic activity and estrogens fate.

In this study, the biodegradation of endocrine-disrupting chemicals (EDCs) (namely the natural and synthetic estrogens 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2), respectively) was assessed in an aerobic granular sludge (AGS) sequencing batch reactor (SBR) treating simulated domestic sewage. To better understand the fate of these compounds, their concentrations were determined in both liquid and solid (biomass) samples. Throughout the operation of the reactor, subjected to alternating anaerobic and aerated conditions, the removal of the hormones, both present in the influent at a concentration of 20 µg L-1, amounted to 99% (for E2) and 93% (for EE2), with the latter showing higher resistance to biodegradation. Through yeast estrogen screen assays, an average moderate residual estrogenic activity (0.09 µg L-1 EQ-E2) was found in the samples analysed. E2 and EE2 profiles over the SBR cycle suggest a rapid initial adsorption of these compounds on the granular biomass occurring anaerobically, followed by biodegradation under aeration. A possible sequence of steps for the removal of the micropollutants, including the key microbial players, was proposed. Besides the good capability of the AGS on EDCs removal, the results revealed high removal efficiencies (>90%) of COD, ammonium and phosphate. Most of the incoming organics (>80%) were consumed under anaerobic conditions, when phosphate was released (75.2 mgP L-1). Nitrification and phosphate uptake took place along the aeration phase, with effluent ammonium and phosphate levels around 2 mg L-1. Although nitrite accumulation took place over the cycle, nitrate consisted of the main oxidized nitrogen form in the effluent. The specific ammonium and phosphate uptake rates attained in the SBR were found to be 3.3 mgNH4+-N gVSS-1.h-1 and 6.7 mgPO43--P gVSS-1 h-1, respectively, while the specific denitrification rate corresponded to 1.0 mgNOx--N gVSS-1 h-1.

Atividade estrogênica de desreguladores endócrinos em águas superficiais do município de Santa Maria Madalena, Sudeste do Brasil / Estrogenic activity of endocrine disruptors in the surface water of Santa Maria Madalena, Southeastern Brazil

RESUMO Nas últimas décadas se intensificou o lançamento, no meio hídrico, de contaminantes com capacidade de desregulação endócrina. Nesse contexto, a aplicação e o aprimoramento de métodos analíticos eficientes passam a ser cada vez mais requeridos para verificar os potenciais impactos dessas substâncias sobre os organismos a elas expostos. Bioensaios podem ser conduzidos para esse fim, como, por exemplo, o ensaio in vitro yeast estrogen screen (YES), que permite a detecção de compostos estrogênicos e citotóxicos. Este estudo, aplicando tal ensaio, investigou a atividade estrogênica das águas e seus potenciais riscos à biota aquática de dois corpos hídricos do município de Santa Maria Madalena, no estado do Rio de Janeiro, Sudeste do Brasil. Observou-se atividade estrogênica apenas no córrego São Domingos, com concentrações de equivalente estradiol (EQ-E2) de 23 e 10.4 ng.L−1 no período de estiagem e chuvoso, respectivamente. Os potenciais riscos desse nível de atividade estrogênica foram mensurados por meio de uma avaliação de risco, que revelou alto e médio risco nas estações seca e chuvosa, respectivamente. Cabe mencionar que, entre os corpos hídricos estudados, a área do córrego São Domingos é aquela com maior adensamento populacional e menor cobertura de coleta e tratamento de esgotos. O ensaio YES mostrou ser uma boa ferramenta para a detecção da presença de desreguladores endócrinos estrogênicos, que pode subsidiar o avanço do conhecimento de corpos hídricos e a formulação de legislação e regulamentações da área ambiental.

ABSTRACT In recent decades, the release of contaminants with endocrine disrupting capacity into the water environment has intensified. In this context, the application and improvement of efficient analytical methods are increasingly required to verify the potential impacts of these substances on the organisms exposed to them. Bioassays can be conducted with this purpose, such as the yeast estrogen screen (YES) in vitro assay, which allows the detection of estrogenic and cytotoxic compounds. This study, applying the YES assay, investigated the estrogenic activity and its potential risks to the aquatic biota of two streams in Santa Maria Madalena, Rio de Janeiro State, Southeastern Brazil. Estrogenic activity was observed only in São Domingos stream, with estradiol equivalent (EEQ) concentrations of 23 and 10.4 ng.L−1 during the dry and rainy season, respectively. The potential risks of this level of estrogenic activity were evaluated by a risk assessment, which revealed a high and medium risk to the local biota in the dry and rainy seasons, respectively. Among the studied water bodies, São Domingos watershed has a bigger population density and less sewage collection and treatment comparatively to Ribeirão Santíssimo stream. The YES assay presented itself as a useful tool for spotting estrogenic endocrine disruptors, with the potential to help in expanding knowledge about water bodies and to create and enforce environmental legislation and regulations.

LED irradiated photo-Fenton for the removal of estrogenic activity and endocrine disruptors from wastewater treatment plant effluent.

The goal of this work was to evaluate the performance of the LED irradiated photo-Fenton process on the removal of (i) estrogenic activity and (ii) seven endocrine disruptors (EDs) (4-octylphenol, 4-nonylphenol, bisphenol A, estrone, 17ß-estradiol, 17α-ethinylestradiol, and estriol) from real wastewater treatment plant effluent (WWTPE). EDs are a group of contaminants of emerging concern present in WWTPE and which may be recognized by hormone receptors, thus harming animal and human health. The yeast estrogenic screen test (YES) was used to quantify estrogenic activity promoted by EDs in WWTPE samples before and after photo-Fenton treatment. Tests were performed following a factorial design with different iron (20, 40, and 60 mg L-1) and hydrogen peroxide (100, 200, and 300 mg L-1) concentrations in a laboratory scale LED photoreactor (λ = 455 nm, 1.5 L, 1.6 × 10-6 Einstein s-1). EDs were analyzed by gas chromatography coupled to a mass spectrometer. Control experiments consisted of Fenton process, iron only, LED irradiation only, and H2O2 only. Optimum experimental conditions for LED photo-Fenton resulted in 62% removal of estrogenic activity and 59% mineralization. In addition, treated WWTPE was not toxic to Aliivibrio fischeri and more than 80% of EDs were removed during LED irradiated photo-Fenton. Although Fenton process showed similar efficiency to that obtained by LED photo-Fenton, a higher volume of sludge was generated in the dark. Finally, results obtained in this study confirm the applicability of LED irradiated photo-Fenton process for improving the quality of WWTPE as an alternative to solar photo-Fenton in case solar radiation is not available, thus reducing hazards associated to WWTPE reuse or discharge.

Comparative endocrine disrupting compound removal from real wastewater by UV/Cl and UV/H2O2: Effect of pH, estrogenic activity, transformation products and toxicity.

Extensive use of endocrine disruptor compounds (EDCs) and their release through various pathways into the environment are emerging environmental concerns. In this context, H2O2 and chlorine UV-based treatments were carried out to evaluate their efficiency in the removal of the bisphenol A (BPA), 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) at 100 µg L-1 from ultrapure water and from wastewater treatment plants (WWTP). Photolysis was performed under different irradiation sources, i.e. UVC and UVA. The effect of H2O2 (3 and 30 mg·L-1), free chlorine concentrations (1 and 2 mg·L-1) and pH (5, 7 and 9) were also investigated. Toxicity (Raphidocelis subcapitata) and estrogenic activity (yeast estrogen screen - YES assay) were assessed during the processes. Compound removal at optimal operating parameters reached 100% after 15 and 2 min for UVC/H2O2 (pH 9 and 3 mg L-1 of H2O2), and UVC/Cl (pH 9 and 2 mg L-1 of chlorine), respectively. Total organic carbon (TOC) removal achieved 37% and 45% for the H2O2 and Cl-UV based process, respectively. The in vitro YES assay indicated that the formed by-products were non-estrogenic compounds, while the toxicity evaluation revealed high cell growth inhibition due to UVC/Cl byproducts. During the UV-based processes, 30 transformation products (TPs) were identified, in which three new chlorinated TPs from E2 and EE2 may be responsible for toxicity effects. EDC degradation by UV/Cl is faster than by UV/H2O2, although chlorinated toxic byproducts were also formed during the UV/Cl process.

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.).

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL-1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.

Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen.

Hypoxic-ischemic brain injury is a complex network of factors, which is mainly characterized by a decrease in levels of oxygen concentration and blood flow, which lead to an inefficient supply of nutrients to the brain. Hypoxic-ischemic brain injury can be found in perinatal asphyxia and ischemic-stroke, which represent one of the main causes of mortality and morbidity in children and adults worldwide. Therefore, knowledge of underlying mechanisms triggering these insults may help establish neuroprotective treatments. Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators exert several neuroprotective effects, including a decrease of reactive oxygen species, maintenance of cell viability, mitochondrial survival, among others. However, these strategies represent a traditional approach of targeting a single factor of pathology without satisfactory results. Hence, combined therapies, such as the administration of therapeutic hypothermia with a complementary neuroprotective agent, constitute a promising alternative. In this sense, the present review summarizes the underlying mechanisms of hypoxic-ischemic brain injury and compiles several neuroprotective strategies, including Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators, which represent putative agents for combined therapies with therapeutic hypothermia.

Evaluation of reduction estrogenic activity in the combined treatment of landfill leachate and sanitary sewage.

Combined treatment of urban solid waste leachate and domestic sewage has emerged in Brazil and worldwide as an alternative to minimize the difficulties of treating landfill leachate. Landfill leachate is a complex matrix of organic and inorganic substances, recalcitrant material and xenobiotic organic compounds that are considered to be highly toxic, as well as endocrine disrupting compounds (EDC) that contribute to increased estrogenic activity. Although combined treatment is feasible for removal of organic matter, ammonia and toxicity, the efficiency of the removal of estrogenic substance is poorly investigated. In this study, the activated sludge process in batch and continuous modes was used for the combined treatment of 2% and 5% leachate/sewage mixtures. Estrogenic activity was reduced in reactors in both batch and continuous modes. The activated sludge process achieved average reductions of the estradiol equivalent (EQ-E2) values in the combined treatment of 94.5, 60.8 and 66.4% for the sanitary sewage, 2% mixture leachate in sewage and 5% mixture leachate in sewage reactors, respectively, in batch mode. For continuous reactors, 86%, 72%, and 65% of reduction of EQ-E2were achieved for sanitary sewage, 2 and 5% mixture with sanitary sewage. As for EQ-E2, the increase in the concentration of leachate in the sewage mixture was detrimental to the removal of estrogenic compounds during the biological process. Therefore, a limit on the % leachate/sewage mixtures should be established to achieve efficiency in the combined treatment of leachate in a Wastewater Treatment Plant (WWTP).

Determination of water quality, toxicity and estrogenic activity in a nearshore marine environment in Rio de Janeiro, Southeastern Brazil.

Endocrine disrupting compounds (EDCs) can be found in domestic sewage, wastewater treatment plant effluents, natural water, rivers, lakes and in the marine environment. Jurujuba Sound, located in the state of Rio de Janeiro, Southeastern Brazil, receives untreated sewage into its waters, one the main sources of aquatic contamination in this area. In this context, the aim of the present study was to evaluate the estrogenic potential of water sampled from different depths and from areas with differential contamination levels throughout Jurujuba Sound. Water quality was evaluated and acute toxicity assays using Allviibrio fischeri were conducted, while estrogenic activity of the water samples was determined by a Yeast Estrogen Screening assay (YES). Water quality was mostly within the limits established for marine waters by the Brazilian legislation, with only DOC and ammoniacal nitrogen levels above the maximum permissible limits. No acute toxicity effects were observed in the Allivibrio fisheri assay. The YES assay detected moderate estrogenic activity in bottom water samples from 3 sampling stations, ranging from 0.5 to 3.2ngL-1, as well as in one surface water sample. Estrogenic activity was most frequently observed in samples from the bottom of the water column, indicating adsorption of estrogenic compounds to the sediment.

Tibolone protects T98G cells from glucose deprivation.

The steroidal drug Tibolone is used for the treatment of climacteric symptoms and osteoporosis in post-menopausal women. Although Tibolone has been shown to exert neuroprotective actions after middle cerebral artery occlusion, its specific actions on glial cells have received very little attention. In the present study we have assessed whether Tibolone exerts protective actions in a human astrocyte cell model, the T98G cells, subjected to glucose deprivation. Our findings indicate that Tibolone decreases the effects of glucose deprivation on cell death, nuclear fragmentation, superoxide ion production, mitochondrial membrane potential, cytoplasmic calcium concentration and morphological parameters. These findings suggest that glial cells may participate in the neuroprotective actions of Tibolone in the brain.

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31 percent), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53 percent). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

Preliminary assessement of the estrogenic potential of Apuleia leiocarpa (Vogel) J.F. Macbr., Fabaceae, Platypodium elegans Vogel, Fabaceae, and Brosimum guianense (Aubl.) Huber, Moraceae, on the wistar rat reproductive system / Avaliação preliminar do potencial estrogênico de Apuleia leiocarpa (Vogel) J.F. Macbr., Fabaceae, Platypodium elegans Vogel, Fabaceae, and Brosimum guianense (Aubl.) Huber, Moraceae, no sistema reprodutor de ratos Wistar

A group of primates (Alouatta guariba) was studied in its natural habitat, where a drastic populational reduction was detected. It is suspected that this reduction is due to the inhibition of fertility caused by the consumption of Apuleia leiocarpa (Vogel) J.F. Macbr., Fabaceae, Platypodium elegans Vogel, Fabaceae, and Brosimum guianense (Aubl.) Huber, Moraceae. These plants are reported to have cumarins, which have been shown to affect ovarian follicular development in rats. This work investigates the estrogenic activity of these plants on the uterus and vagina using castrated rats as the biological model. Pubescent castrated rats were treated for five days with A. leiocarpa, P. elegans and B. guianense hydroalcoholic extracts (50 mg/rat). Uterus and pituitary gland weight, vaginal cornification and opening were evaluated. The results showed that the administration of the extracts did not significantly alter the parameters analyzed. This preliminary investigation indirectly indicates the absence of estrogenic effect on the rat reproductive system and no relation to the populational reduction of this particular group of primates.

Um grupo de primatas da espécie Alouatta guariba foi estudado em seu habitat natural na Mata Atlântica, onde foi observada uma drástica redução populacional dessa espécie. Suspeita-se que essa redução se deve à inibição da fertilidade das fêmeas devido ao consumo de Apuleia leiocarpa (Vogel) J.F. Macbr., Fabaceae, Platypodium elegans Vogel, Fabaceae e Brosimum guianense (Aubl.) Huber, Moraceae. Estudos fitoquímicos indicaram a presença de cumarinas, especialmente em B. guianense e P. elegans, cujo efeito adverso no desenvolvimento de folículos ovarianos foi previamente relatado em ratas. Este trabalho investiga a atividade estrogênica dessas plantas no útero e vagina utilizando ratas castradas como modelo experimental. Ratas Wistar pubescentes castradas foram tratadas por cinco dias com os extratos hidroalcoólicos de A. leiocarpa, P. elegans and B. guianense (50 mg/rata). Foram analisados os seguintes parâmetros: peso de útero e hipófise, cornificação e abertura vaginal. Os resultados preliminares obtidos mostraram que a administração dos extratos não alterou significativamente as variáveis analisadas, indicando, indiretamente, a ausência de efeito estrogênico no sistema reprodutor das ratas tratadas com as plantas citadas. Esses dados sugerem que o consumo dessas plantas não está relacionado com a redução populacional observada no grupo de primatas da espécie A. guariba.

Semente de linhaça e o efeito de seus compostos sobre as células mamárias / Flaxseed and the effect of his compound on human breast cell

O câncer de mama é uma doença que afeta principalmente as mulheres e segundo as estatísticas esta vem aumentando com certa frequência nos países ocidentais, e isto tem preocupado a comunidade científica. Esta doença está associada a diversos fatores de risco, sendo a dieta um fator que tem demonstrado relação com a promoção de câncer de mama. Uma alimentação rica em substância funcional tem sido alvo de atenção, pois os fitoestrógenos têm mostrado através de estudos experimentais, propriedades benéficas à saúde, e parece contribuir para a redução do risco de câncer de mama. Alimentos como a semente de linhaça tem sido objeto de estudo, já que contêm substâncias consideradas como quimioprotetora e sua estrutura química assemelha-se ao estrogênio humano e compete com este pelo seu sítio de ligação. De acordo com os estudos experimentais, realizados com animais e humanos, a semente de linhaça é rica em lignana e outros componentes, que apresentaram ter efeito fracamente estrogênico e antiestrogênico, mostrando exercer influência na diminuição do risco de câncer de mama.

The breast cancer is a disease that affects especially women, and according to statistics, this is increasing with certain frequency in western country and it has been concerning the scientific society. This disease is associated with various factors of risk, and diets have being considered a factor that has promoted breast cancer. Food rich in functional substances has drawn attention, because phytoestrogens have showed, through experimental studies, beneficial properties for health and appeared to contribute for the decrease of breast cancer risk. Food with flaxseed has been object of study, because it contains substances called chemoprotective and its chemistry structure resembles human estrogens and competes with its link site. According to the experimental studies made in animals and humans, flaxseed is rich in lignans and other components, that seem to have weak estrogenic/antiestrogenic effect showing to exert influence in the decreasing of breast cancer risk.

Reproductive and toxicological effects of isoflavones on female offspring of rats exposed during pregnancy

We investigated the actions of isoflavones (daidzin + daidzein 22.7%, daidzein 16.9%, genistin + genistein 16.3%, genistein 13.1%) in pregnant rats, assessing possible repercussions regarding the development of female conceptus. Doses of isoflavones, 10 mg/kg or 100 mg/kg, were administered to pregnantrats by oral gavage, from the sixth day of pregnancy until its completion. The pregnant rats exposed to isoflavones at these doses when laparotomized showed alterations in the number of live fetuses, lysed fetuses, number of resorption sites, and implantation sites. In the pregnant rats, no maternal toxicity was observed, despite presenting a significant anticipation of the offspring birth date. The rats belonging to the isoflavones 10 mg/kg and 100 mg/kg groups also gave birth to a smaller number of offspring. In female offspring, the parameters for presenting pelage, eyes opening, ears unfolding, and age for onset of puberty occurred early. At adult life, despite not observing any difference in the number of estruses, irregularities in estrous cycle including prolongation of the estrus phase in hours were observed in the group exposed to 10 mg/kg of isoflavones. These results indicate that isoflavones, despite presenting weak estrogenic activity, were able to interfere in sexual and bodily development, resulting in reproductive alterations. Extensive studies should be done, aiming to evaluate the possible effects of isoflavones in this critical development period.

Reproductive and toxicological effects of isoflavones on female offspring of rats exposed during pregnancy

We investigated the actions of isoflavones (daidzin + daidzein 22.7%, daidzein 16.9%, genistin + genistein 16.3%, genistein 13.1%) in pregnant rats, assessing possible repercussions regarding the development of female conceptus. Doses of isoflavones, 10 mg/kg or 100 mg/kg, were administered to pregnantrats by oral gavage, from the sixth day of pregnancy until its completion. The pregnant rats exposed to isoflavones at these doses when laparotomized showed alterations in the number of live fetuses, lysed fetuses, number of resorption sites, and implantation sites. In the pregnant rats, no maternal toxicity was observed, despite presenting a significant anticipation of the offspring birth date. The rats belonging to the isoflavones 10 mg/kg and 100 mg/kg groups also gave birth to a smaller number of offspring. In female offspring, the parameters for presenting pelage, eyes opening, ears unfolding, and age for onset of puberty occurred early. At adult life, despite not observing any difference in the number of estruses, irregularities in estrous cycle including prolongation of the estrus phase in hours were observed in the group exposed to 10 mg/kg of isoflavones. These results indicate that isoflavones, despite presenting weak estrogenic activity, were able to interfere in sexual and bodily development, resulting in reproductive alterations. Extensive studies should be done, aiming to evaluate the possible effects of isoflavones in this critical development period.(AU)