Embryotoxic Effects of Pesticides in Zebrafish (Danio rerio): Diflubenzuron, Pyriproxyfen, and Its Mixtures.

Diflubenzuron (DFB) and pyriproxyfen (PPF) are larvicides used in crops to control insect plagues. However, these pesticides are known to impact non-target organisms like fish and mammals. Here, we aimed at assessing the embryotoxicity of purified DFB, PPF, and their mixtures in a non-target organism-zebrafish. Zebrafish embryos were exposed to different concentrations for 120 h: 0.025, 0.125, 0.25, 1.25, 2.5, and 10 mg/L of purified PPF and purified DFB, while we used 0.025 mg/L PPF + 10 mg/L DFB (Mix A), 0.125 mg/L PPF + 10 mg/L DFB (Mix B), and 0.25 mg/L PPF + 10 mg/L DFB (Mix C) for the mixtures of PPF + DFB. We observed mortality, teratogenicity, and cardiotoxicity. For the neurotoxicity tests and evaluation of reactive oxygen species (ROS) levels in the brain, embryos were exposed for 120 h to 0.379 and 0.754 mg/L of PPF and 0.025 and 0.125 mg/L of DFB. We established the LC50 for PPF as 3.79 mg/L, while the LC50 for DFB was not determinable. Survival and hatching were affected by PPF concentrations above 0.125 mg/L, DFB concentrations above 1.25 mg/L, and the lower pesticide mixtures. PPF exposure and mixtures induced different types of malformations, while a higher number of malformations were observed for the mixtures, suggesting a potentiating effect. Pesticides diminished avoidance responses and increased the levels of ROS across all concentrations, indicating neurotoxicity. Our findings underscore the detrimental impact of PPF and DFB exposure, spanning from biochemistry to morphology. There is a critical need to reconsider the global use of these pesticides and transition to more ecologically friendly forms of pest control, raising an alarm regarding repercussions on human and animal health and well-being.

The First Steps on AOPs' Concepts, Development, and Applications in Teratology.

An Adverse Outcome Pathway (AOP) is an analytical model that describes, through a graphical representation, a linear sequence of biologically connected events at different levels of biological organization, causally leading to an adverse effect on human health or the environment. In general, AOPs are constructed based on five central principles: systematic development and review, chemical-agnostic, modular, networks, and living documents. Furthermore, AOPs have the potential to be used, for example, to investigate certain molecular targets; relate the regulation of specific genes or proteins among AOPs; extrapolate biological processes, pathways, or diseases from one species to another; and even predict adverse effects in particular populations. AOPs also emerge as an alternative to animal experimentation in studies of developmental malformations. It's even possible now to develop a quantitative AOP to predict teratogenic effects for some substances. However, the construction of high-quality AOPs requires standardization in the way these models are developed and reviewed, ensuring an adequate degree of flexibility and guaranteeing efficiency. The development of AOPs should strictly be based on the guidance documents developed by the OECD. Nevertheless, an important step for those developing AOPs is the choice of an apical endpoint or an initiating molecular event in order to initiate the construction of the pathway. Another crucial step is a systematic literature review based on the random combination of the blocks of information. With these two fundamental steps completed, it only remains to follow the guidance documents on Developing and Assessing Adverse Outcome Pathways and AOP Developers' Handbook supplement provided by the OECD to organize and construct an AOP. This modern approach will bring radical changes in the field of toxicity testing, regarding the prediction of apical toxic effects using molecular-level effects.

Maternal-fetal safety evaluation of an aqueous extract of Casearia sylvestris leaves in rats.

BACKGROUND: This study evaluated the maternal, embryotoxic, and teratogenic effects of the aqueous extract of Casearia sylvestris (AECS), a species listed in the Unique Health System of Brazil, and widely used for treating several conditions, such as diarrhea, wounds, pain, and ulcers. METHODS: Pregnant rats were daily treated orally with 0, 175, 350, or 700 mg/kg/body weight of AECS, from gestational day (GD) 6 to 15 (organogenesis period). On GD 20, the pregnant rats were euthanized, and the litters submitted to an assessment of fetal development. RESULTS: No clinical signs of toxicity were observed in the dams during the treatment. In the embryo-fetal development study, a significant increase in the basal zone height of the placenta was observed in the intermediate dose group. Furthermore, there was a significant increase in the relative anogenital distance measurement of female fetuses in the lowest and intermediate dose groups. Although no visceral abnormalities were observed in the treated-fetuses, skeletal anomalies evidenced by changes in the ossification of the sternum and the presence of supernumerary ribs were found in the intermediate and high dose groups. CONCLUSION: In conclusion, the treatment with AECS during organogenesis at this dose level had detrimental effects on the normal development of fetuses.

Embryo-fetal safety evaluation of ondansetron in rats.

BACKGROUND: Ondansetron is a 5HT3 receptor antagonist, used to mitigate the effects of nausea and vomiting after chemotherapy or surgery. Since nausea and vomiting are common experiences during the first trimester of pregnancy, this antiemetic has been the main drug used during this period. METHODS: To evaluate the effects of ondansetron on the embryo-fetal development, which are still very contradictory, pregnant rats were exposed to therapeutic doses of ondansetron (1.7 or 2.5 mg/kg) daily, from gestational day (GD) 6 to 15. RESULTS: No clinical signs of toxicity were observed in dams during the treatment. Although the hemato-biochemical parameters were similar among the groups, histological changes, as well as a reduction in the weight of kidney were found in the treated dams. After fetal examination, no visceral and skeletal abnormalities were observed in treated fetuses. CONCLUSION: In conclusion, therapeutic doses of ondansetron have low teratogenic potential in rats. These data provide important information about the drug safety during pregnancy.

Toxicological effects of the Morinda citrifolia L. fruit extract on maternal reproduction and fetal development in rats.

Morinda citrifolia L., also known as Noni, is widely used plant in folk medicine for various therapeutic purposes. However, reports on its effects during pregnancy are limited. Therefore, the objective of this study was to evaluate the effects of the M. citrifolia fruit extract on maternal performance and fetal development during pregnancy in rats. Pregnant Wistar rats (n = 12/group) were treated from gestational days (GD) 0-21 with water (control group) or the aqueous extract of M. citrifolia fruit at doses of 200, 400, or 750 mg/kg, orally. During pregnancy, clinical signs of toxicity, maternal weight, feed intake, and water consumption were noted. On GD 21, the rats were anesthetized and blood was collected to evaluate various biochemical parameters. During laparotomy, reproductive performance parameters were recorded, and fetuses were weighed and the anomalies analyzed. Reduced placental efficiency and fetal growth restriction were observed in the group treated with 400 mg/kg of M. citrifolia extract. The highest dose (750 mg/kg) augmented aspartate aminotransferase concentration and preimplantation losses, while reducing the number of live fetuses. Furthermore, both doses (400 and 750 mg/kg) of the plant extract caused fetal anomalies. In conclusion, consumption of high doses of the M. citrifolia aqueous extrac during pregnancy leads to maternal hepatotoxicity, anti-implantation effects, intrauterine growth restriction and fetal abnormalities, indicating that the plant fruit extract can be harmful to both the mother and the fetus.

Antiseizure medication in early nervous system development. Ion channels and synaptic proteins as principal targets.

The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk. For this reason, the pharmacological treatments of the pregnant Women with Epilepsy (WWE) need comprehensive analyses to reduce fetal risk during the first trimester of pregnancy. The mechanisms by which ASM are teratogens are still under study and scientists in the field, propose different hypotheses. One of them, which will be addressed in this review, corresponds to the potential alteration of ASM on ion channels and proteins involved in relevant signaling and cellular responses (i.e., migration, differentiation) during embryonic development. The actual information related to the action of ASM and its possible targets it is poorly understood. In this review, we will focus on describing the eventual presence of some ion channels and synaptic proteins of the neurotransmitter signaling pathways present during early neural development, which could potentially interacting as targets of ASM. This information leads to elucidate whether these drugs would have the ability to affect critical signaling during periods of neural development that in turn could explain the fetal malformations observed by the use of ASM during pregnancy.

Multi-biomarker approach and IBR index to evaluate the effects of bisphenol A on embryonic stages of zebrafish (Danio rerio).

This study assessed the effects of Bisphenol A in embryonic stages of zebrafish, applying an IBR multi-biomarker approach that included alterations in growth and oxidative status and relates it with the expression of Nrf1, Nrf2, Wnt3a, Wnt8a, COX-2, Qdpra, and DKK1 genes. For this purpose, we exposed zebrafish embryos to eight environmentally relevant concentrations of BPA (220, 380, 540, 700, 860, 1180, 1340, and 1500 ng L-1) until 96 h post-fertilization. Our results show that BPA induces several malformations in embryos (developmental delay, hypopigmentation, tail malformations, and on), leading to their death. The LC50, EC50 of malformations, and teratogenic index (TI) were 1234.60 ng L-1, 987.77 ng L-1, and 1.25, respectively; thus, this emerging contaminant is teratogenic. Regarding oxidative stress and gene expression, we demonstrated BPA altered oxidative status and the gene expression in embryos of Danio rerio.

Evaluation of the developmental toxicity of solvents, metals, drugs, and industrial chemicals using a freshwater snail (Biomphalaria glabrata) assay.

A freshwater snail assay was employed to assess the embryotoxicity of solvents including acetone, methanol, ethanol, isopropanol, dimethyl-sulfoxide, glycerin, metals/metalloids including mercuric chloride (HgCl2), cadmium chloride (CdCl2,), antimony salts Sb+3 and Sb+5, drugs including colchicine, hydroxyurea, cyclophosphamide, an industrial chemical sodium azide (SA), an anionic surfactant dodecyl sodium sulfate-(DSS), H2O2 and sodium chloride (NaCl). The assay consists of exposing Biomphalaria glabrata egg masses (EM) to the substances for 96-hr and following up embryo/snail development for lethality, abnormal morphology (teratogenicity), and day of hatching up to day 10 or 14 after spawning. Based upon concentration-response relationships, LC50%s (embryolethality), EC50%s (teratogenicity) and IC50%s (hatching retardation) and 95%CIs were determined for tested chemicals. The LOECs indicated that HgCl2 (37 nM) and CdCl2 (140 nM) are potent embryotoxic agents in snails. Teratogenic indices (TI = LC50/EC50) for almost all tested chemicals were lower than or close to unity suggesting that these compounds were not teratogenic in this assay. The snail assay may be adequately performed in a cost-effective standardized protocol which enables testing a number of environmental chemicals over a broad concentration range. The snail assay needs to undergo further validation to be recognized for an internationally harmonized hazard identification in ecotoxicity risk assessment.

Effects of Prenatal Exposure to Aflatoxin B1: A Review.

Aflatoxins are mycotoxins produced as secondary fungal metabolites. Among them, aflatoxin B1 (AFB1) stands out due to its genotoxic and mutagenic potential, being a potent initiator of carcinogenesis. In this review, the outcomes from the published literature in the past 10 years on the effects of AFB1 pathophysiological mechanisms on embryological and fetal development are discussed. In several animal species, including humans, AFB1 has a teratogenic effect, resulting in bone malformations, visceral anomalies, lesions in several organs, and behavioral and reproductive changes, in addition to low birth weight. The mutagenic capacity of AFB1 in prenatal life is greater than in adults, indicating that when exposure occurs in the womb, the risk of the development of neoplasms is higher. Studies conducted in humans indicate that the exposure to this mycotoxin during pregnancy is associated with low birth weight, decreased head circumference, and DNA hypermethylation. However, as the actual impacts on humans are still unclear, the importance of this issue cannot be overemphasized and studies on the matter are essential.

Effects of benzo(a)pyrene at environmentally relevant doses on embryo-fetal development in rats.

Studies have demonstrated that Benzo(a)Pyrene (BaP), a polycyclic aromatic hydrocarbon ubiquituous in the environment, can cause teratogenic effects. Since the majority of studies used in vitro models or high doses of BaP, this study evaluated the teratogenicity, reproductive and developmental performance of low doses of BaP through maternal and fetus examination after daily oral administration of BaP (0; 0.1; 1.0 or 10 µg/kg) to pregnant Wistar rats from Gestational day (GD) 6 to GD 15 (the organogenesis period). Pregnant rats did not exhibit clinical signs of toxicity during the exposure period. However, dams exposed to the lowest dose of BaP showed a reduction in the erythrocytes number and in the creatinine levels. The groups exposed to 0.1 and 1.0 µg/kg presented a decrease in placental efficiency, as well as an increase in placental weight. After fetal examination, the treated group with the lowest dose showed a reduced relative anogenital distance, while the curve of normal distribution of weight was changed in the highest dose group. In addition, anomalies evidenced by changes in the renal size and degree of fetal ossification were observed in treated-fetus. In conclusion, treatment with BaP during organogenesis at this dose level is detrimental to the normal development of fetuses.

Avaliação da toxicidade pré-natal: estudo de teratogenicidade do inseticida piriproxifeno em ratos Wistar / Prenatal toxicity assessment: teratogenicity study of the insecticide pyriproxyfen in Wistar rats

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)

This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)

Avaliação da toxicidade pré-natal: estudo de teratogenicidade do inseticida piriproxifeno em ratos Wistar / Prenatal toxicity assessment: teratogenicity study of the insecticide pyriproxyfen in Wistar rats

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)

This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)

Efeitos tóxicos dos sedimentos do estuário do rio Capibaribe em embriões de zebrafish (Danio rerio) / Toxic effects of sediments of the Capibaribe estuary on zebrafish embryos (Danio rerio)

O presente estudo utilizou embriões de Danio rerio expostos aos elutriatos dos sedimentos estuarinos do rio Capibaribe, dos períodos chuvoso e seco, e analisou os efeitos letais, teratogênicos, bem como a frequência cardíaca. Os testes de toxicidade com os embriões seguiram as diretrizes da OECD 236. Mediante os resultados obtidos, a frequência cardíaca e a teratogenicidade foram os efeitos mais observados nos animais quando submetidos às amostras. Entre os efeitos teratogênicos, o retardo geral no desenvolvimento dos embriões foi o mais frequente durante as análises. Tais efeitos tóxicos se modificaram entre os pontos e entre os períodos de coleta. Essa variação de toxicidade pode estar relacionada à diversidade de atividades realizadas no entorno desse estuário, a influência do regime de chuvas, marés e correntes, indicando que a análise dos efeitos subletais e da teratogenicidade em embriões de D. rerio constitui bom parâmetro para avaliações de toxicidade de amostras ambientais.(AU)

The present study used Danio rerio embryos exposed to the elutriates of the estuarine sediments of the Rio Capibaribe, from the rainy and dry periods, where the lethal effects, teratogenic and heart rate were analyzed. Embryotoxicity tests followed the guidelines of OECD 236. Based on the results obtained, heart rate and teratogenicity demonstrated higher sensitivity to the samples. Among the teratogenic effects, the general delay in embryo development was the most frequent effect during the analyzes. These toxic effects changed between the points and between the collection periods. This variation of toxicity may be related to the diversity of activities carried out around this estuary, the influence of rainfall, tides, and currents, indicating the analysis of sublethal effects and teratogenicity in the D. rerio embryos are useful parameters for toxic evaluation of environmental samples.(AU)

Efeitos tóxicos dos sedimentos do estuário do rio Capibaribe em embriões de zebrafish (Danio rerio) / Toxic effects of sediments of the Capibaribe estuary on zebrafish embryos (Danio rerio)

O presente estudo utilizou embriões de Danio rerio expostos aos elutriatos dos sedimentos estuarinos do rio Capibaribe, dos períodos chuvoso e seco, e analisou os efeitos letais, teratogênicos, bem como a frequência cardíaca. Os testes de toxicidade com os embriões seguiram as diretrizes da OECD 236. Mediante os resultados obtidos, a frequência cardíaca e a teratogenicidade foram os efeitos mais observados nos animais quando submetidos às amostras. Entre os efeitos teratogênicos, o retardo geral no desenvolvimento dos embriões foi o mais frequente durante as análises. Tais efeitos tóxicos se modificaram entre os pontos e entre os períodos de coleta. Essa variação de toxicidade pode estar relacionada à diversidade de atividades realizadas no entorno desse estuário, a influência do regime de chuvas, marés e correntes, indicando que a análise dos efeitos subletais e da teratogenicidade em embriões de D. rerio constitui bom parâmetro para avaliações de toxicidade de amostras ambientais.(AU)

The present study used Danio rerio embryos exposed to the elutriates of the estuarine sediments of the Rio Capibaribe, from the rainy and dry periods, where the lethal effects, teratogenic and heart rate were analyzed. Embryotoxicity tests followed the guidelines of OECD 236. Based on the results obtained, heart rate and teratogenicity demonstrated higher sensitivity to the samples. Among the teratogenic effects, the general delay in embryo development was the most frequent effect during the analyzes. These toxic effects changed between the points and between the collection periods. This variation of toxicity may be related to the diversity of activities carried out around this estuary, the influence of rainfall, tides, and currents, indicating the analysis of sublethal effects and teratogenicity in the D. rerio embryos are useful parameters for toxic evaluation of environmental samples.(AU)

Polymethoxy-1-Alkenes Screening of Chlorella and Spirulina Food Supplements Coupled with In Vivo Toxicity Studies.

Selected species of cyanobacteria and green algae have been reported to produce lipophilic polymethoxy-1-alkenes (PMAs) which were shown to exhibit in vivo teratogenicity. Considering that information on PMAs in Arthospira sp. (known commercially as Spirulina) and Chlorella sp. cultivated for food supplement production was essentially lacking, the present study screened Chlorella (n = 10) and Spirulina (n = 13) food supplements registered in the European Union. Mass spectrometry analysis of column fractionated extracts was performed. None of the four variants previously reported in some cyanobacteria and green algae, nor any potentially related structures were detected in the studied samples. Since the isolated lipophilic fractions contained various compounds, they were further screened for in vivo teratogenicity in Danio rerio embryo, and for the potential to induce oxidative stress and genotoxicity in the liver and neurotoxicity in the brain of adult zebrafish. None of the tested food supplements had detectable levels of PMAs or any potentially related structures. No teratogenicity was revealed except for spinal curvature induced by fractions obtained from two Chlorella products. Selected fractions revealed cytotoxicity as indicated by an increased level of reactive oxygen species, catalase activity, lipid peroxidation and increased frequency of DNA strand breaks in hepatic tissue. The majority (60%) of Chlorella fractions induced an increase in cholinesterase activity in zebrafish brain homogenate while exposure to 61.5% of Spirulina fractions was associated with its decrease. The present study confirms that Chlorella and Spirulina food supplements are free of teratogenic PMAs, although the observed in vivo toxicities raise questions regarding the quality of selected products.

Toxicity characterization and environmental risk assessment of Mancozeb on the South American common toad Rhinella arenarum.

Agricultural activity, especially the increasing use of pesticides, is considered one of the main reasons for the decline of amphibian populations. Mancozeb (MCZ) is one of the most used fungicides worldwide, despite its ancient use and toxicity demonstrated in different taxa. However, there is limited information about the effects of MCZ in amphibians, which are keystones of riparian ecosystems. For species conservation purposes, it is essential to identify the most sensitive developmental period(s) of a given species to a xenobiotic. We evaluated the toxicity of a commercial fungicide of mancozeb, (80% active ingredient) on the early development of the common South American toad Rhinella arenarum (Anura, Bufonidae). Embryos from early blastula (S.4) and larvae from complete operculum (S.25) stages were exposed to a wide range of MCZ concentrations during acute, subchronic and chronic exposure (up to 504 h) periods. The toxicity profiles for lethal and sublethal effects were performed. At all exposure times, MCZ was more toxic to embryos, for instance, NOEC 504 h were 0.01 and 0.05 mg MCZ/L for embryos and larvae, respectively. Thus, embryo sensitivity was 5-fold higher than larvae. A Teratogenic Index of 14 indicated the significant teratogenic potential of this fungicide. Among sublethal effects, embryos exhibited a wide range of abnormalities with high incidence. The ecological risk assessment demonstrated that the estimated Risk Quotient value for Rhinella arenarum embryos at chronic exposure was higher than the Level of Concern value, which warns about the potential risk of MCZ for this native species.

Embryotoxic and teratogenic profile of tretracycline at environmentally relevant concentrations on Cyprinus carpio.

The objective of this work was to evaluate whether tetracycline (TC) in environmentally relevant concentrations was able to induce alterations to embryonic development and teratogenic effects in oocytes and embryos of Cyprinus carpio. For this purpose, an embryolethality study was conducted and the lethal concentration 50 (LC50) and effective concentration 50 of malformations (EC50) were calculated, and with these data the teratogenic index (TI) was determined. The main alterations to embryonic development and the teratogenic effects produced by TC on embryos of C. carpio were determined using the Kimmel and Hersem scale adapted for Cyprinus carpio. LC50 and EC50 were respectively 500.08 and 145.3 µg L-1.TC was shown to be teratogenic with teratogenic index of 3.44, and the main malformations identified in concentrations of 90-900 µg L-1 were malformation in tail, modified chorda structure, pericardical edema, scoliosis and malformations of the heart. A significant decrease in concentration-dependent in Kimmel and Hersem score was observed. The results allow us to conclude that TC at environmentally relevant concentrations is capable of inducing embryotoxic and teratogenic effects, generating risk in the integrity of the common carp C. Carpio.

The zebrafish embryotoxicity test (ZET) for nanotoxicity assessment: from morphological to molecular approach.

Nanotechnology and use of nanomaterials (NMs) improve life quality, economic growth and environmental health. However, the increasing production and use of NMs in commercial products has led to concerns about their potential toxicity on human and environment health, as well as its toxicological classification and regulation. In this context, there is an urgent need to standardize and validate procedures for nanotoxicity testing. Since the zebrafish embryotoxicity test (ZET) has been indicated as a suitable approach for the toxicity assessment of traditional and emergent pollutants, the aim of this review is to summarize the existing literature on embryotoxic and teratogenic effects of NMs on zebrafish. In addition, morphological changes in zebrafish embryos induced by NMs were classified in four reaction models, allowing classification of the mode of action and toxicity of different types of NM. Revised data showed that the interaction and bioaccumulation of NMs on zebrafish embryos were associated to several toxic effects, while the detoxification process was limited. In general, NMs induced delayed hatching, circulatory changes, pigmentation and tegumentary alterations, musculoskeletal disorders and yolk sac alterations on zebrafish embryos. Recommendations for nanotoxicological tests are given, including guidance for future research. This review reinforces the use of the ZET as a suitable approach to assess the health risks of NM exposure.

Polluted water from an urban reservoir (Madín dam, México) induces toxicity and oxidative stress in Cyprinus carpio embryos.

The Madín Dam is a reservoir located in the municipalities of Naucalpan and Atizapán, in the metropolitan area adjacent to Mexico City. The reservoir supplies drinking water to nearby communities and provides an area for various recreational activities, including kayaking, sailing and carp fishing. Over time, the number of specimens of common carp has notably diminished in the reservoir, which receives direct domestic drainage from two towns as well as numerous neighborhoods along the Tlalnepantla River. Diverse studies have demonstrated that the pollutants in the water of the reservoir produce oxidative stress, genotoxicity and cytotoxicity in juvenile Cyprinus carpio, possibly explaining the reduction in the population of this species; however, it is necessary to assess whether these effects may also be occurring directly in the embryos. Hence, surface water samples were taken at five sites and pharmaceutical drugs, personal care products (especially sunscreens), organophosphate and organochlorine pesticides, and other persistent organic pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) were identified. Embryos of C. carpio were exposed to the water samples to evaluate embryolethality, modifications in embryonic development, lipoperoxidation, the quantity of hydroperoxide and oxidized proteins, and antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase). It was found that the polluted water of the Madín Dam gave rise to embryolethality, embryotoxicity, congenital abnormalities, and oxidative stress on the common carp embryos.

Alterations to embryonic development and teratogenic effects induced by a hospital effluent on Cyprinus carpio oocytes.

Hospital functioning generates a great quantity of contaminants, among which organic materials, heavy metals, and diverse pharmaceuticals are noteworthy that can affect organisms if they are not properly removed from the effluents. The hospital effluent evaluated in the present study came from IMSS (Instituto Mexicano del Seguro Social) Clinic 221 in downtown Toluca, State of Mexico, a secondary care facility. The contaminants identified in hospitals have been associated with deleterious effects on aquatic organisms; however, it is necessary to continue with more studies in order to be able to regulate the production of said contaminants which are generally dumped into the city sewage system. The present study had the purpose of evaluating the alterations to embryonic development and teratogenic effects on oocytes Cyprinus carpio after exposure to different proportions of hospital effluent. For said purpose, the physicochemical properties of the effluent were determined. Concentrations of the main microcontaminants were also determined. An embryolethality study out and the determination of the main alterations to embryonic development and teratogenic effects produced, due to exposure of C. carpio at different proportions of the effluent, were carried out. The results showed that the physicochemical properties were within the values permitted by Mexican regulation; however, the presence of contaminants such as NaClO, metals, anti-biotics, anti-diabetics, non-steroidal anti-inflammatory drugs, hormones and beta-blockers, was detected. Lethal concentration 50 was 5.65% and the effective concentration for malformations was 3.85%, with a teratogenic index of 1.46. The main teratogenic alterations were yolk deformation, scoliosis, modified chorda structure, tail malformation, fin deformity and mouth hyperplasia. A high rate of hatching delay was observed. The results suggest that the hospital effluent under study is capable of inducing embryotoxicity and teratogenicity in oocytes of C. carpio.