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Detecting the toxic effects of chemicals on reproduction and development without using mammalian animal models is crucial in the exploitation of pharmaceuticals for human use. Zebrafish are a promising animal model for investigating pharmacological effects and toxicity during vertebrate development. Several studies have suggested the use of zebrafish embryos for the assessment of malformations or embryo-fetal lethality (MEFL). However, a reproducible protocol as a standard for the zebrafish MEFL test method that fulfills global requests has not been established based on the International Council of Harmonisation (ICH) S5 (R3) guidelines. To establish such a toxicity test method, we developed a new and easy protocol to detect MEFL caused by chemicals, especially those with teratogenic potential, using fertilized zebrafish eggs (embryos) within 5 days of development. Our toxicity test trials using the same protocol in two to four different laboratories corroborated the high inter-laboratory reproducibility. Our test method enabled the detection of 18 out of 22 test compounds that induced rat MEFL. Thus, the prediction rate of our zebrafish test method for MEFL was almost 82% compared with that of rat MEFL. Collectively, our study proposes the establishment of an easy and reproducible protocol for the zebrafish MEFL test method for reproductive and developmental toxicity that meets ICH guideline S5 (R3), which can be further considered in combination with information from other sources for regulatory use. [ABSTRACT FROM AUTHOR]

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The effect of the lipid extract isolated from the tunic of the marine hydrobiont Halocynthia aurantium was studied. Its administration during hypothermia, hyperthermia, muscle load, introduction of hexenal, and the vertical fixation by the dorsal neck fold, as well as its embryotoxic and teratogenic effects, was evaluated. The impact of stress (vertical fixation of rats by the dorsal neck fold) was accompanied by an increase in the plasma levels of total lipids, total cholesterol, cholesterol/phospholipid ratios, and a decrease in the total phospholipids, as well as by a change in the quantitative characteristics of classes of neutral and phospholipids. A correction of the developed changes by a lipid extract of ascidia and a commercial reference preparation Omega-3 was carried out. The lipid extract of H. aurantium showed a higher efficiency in restoring the lipid composition of the blood plasma under stress impact compared to the preparation Omega-3 due to the wider range of neutral and phospholipid classes, polyunsaturated fatty acids of the n-3 and n-6 families. The tunic of ascidian can be used as a raw material for obtaining preparations with stress-protector and lipid-correcting properties. [ABSTRACT FROM AUTHOR]

Background: Porcine bile powder (PBP) is a traditional Chinese medicine that has been used for centuries in various therapeutic applications. However, PBP has not previously undergone comprehensive component analysis and not been evaluated for safety through standard in vivo toxicological studies. Methods: In our study, we characterized the component of PBP by liquid chromatography-mass spectrometry. The acute and subchronic oral toxicity, genotoxicity, and teratogenicity studies of PBP were designed and conducted in Kunming mice and Sprague-Dawley (SD) rats. Results: The chemical analysis of PBP showed that the main components of PBP were bile acids (BAs), especially glycochenodeoxycholic acid. There were no signs of toxicity observed in the acute oral test and the subchronic test. In the genotoxicity tests, no positive results were observed in the bacterial reverse mutation test. Additionally, in the mammalian micronucleus test and mouse spermatocyte chromosomal aberration test, no abnormal chromosomes were observed. In the teratogenicity test, no abnormal fetal development was observed. Conclusion: Our findings demonstrate that PBP, composed mainly of BAs, is non-toxic and safe based on the conditions tested in this study. [ABSTRACT FROM AUTHOR]

Abstract Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails’ embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.

Nausea and vomiting of pregnancy (NVP), associated as „morning sickness”, is a problem faced by approximately 70% of pregnant women. The exact mechanism of NVP is not known, research suggests that growth and differentiation factor 15 (GDF 15) secreted by the placenta has a significant impact on these symptoms. Various scales and indices are used to describe the condition in NVP: the PUQE index, the Rhodes index, the McGill nausea questionnaire, and the visual-analogue scale. Depending on the severity of the disease course, therapy may include the non-pharmacological and/or pharmacological sphere. In this article, reports on the treatment of NVP worldwide, therapeutic preparations registered on the Polish market and current recommendations for their safety were presented. Non-pharmacological recommendations for NVP include a change in diet, avoidance of spicy foods, supplementation with preparations containing ginger rhizome or acupressure. Pyridoxine, antihistamines, dopamine D2 receptor antagonists, serotonin 5-HT₃ receptor antagonists and glucocorticosteroids are used to treat vomiting. Despite the wide range of antiemetics, there is still a search for effective NVP therapies, drugs with few side effects and, above all, adequate safety. Multicenter studies on a large population are particularly valuable in assessing teratogenicity, based on which are used to recommend whether a medicine can be used during pregnancy, especially in the first trimester. A two-component product containing pyridoxine and doxylamine was launched on the Polish market in December 2021. This drug was withdrawn from the US market in the 1980s because of suspicions that it was harmful. It is now recommended by both the US Food and Drug Administration and the Polish Society of Obstetricians and Gynaecologists as a first-line treatment for NVP. If treatment with this drug is ineffective, promethazine, in severe cases, metoclopramide and corticosteroids are also used in this indication. In some pregnant women, persistent vomiting leads to dehydration and malnutrition. In these cases, additional fluid therapy and clinical nutrition should be given.

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β‐carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β‐carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child‐bearing age, pregnant and lactating women and post‐menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4–11 months) and 2600 μg RE/day (adolescents 15–17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β‐carotene. The available data were not sufficient and suitable to characterise a dose–response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β‐carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β‐carotene. The use of supplemental β‐carotene by the general population should be limited to the purpose of meeting vitamin A requirements. [ABSTRACT FROM AUTHOR]

Background: The individual teratogenicity profiles of Lumacaftor and Ivacaftor are known, but the combined effects remain unexplored. Purpose: To evaluate the teratogenic profile of a combination of Lumacaftor and Ivacaftor in Sprague-Dawley Rats. Materials and Methods: This study adhered to the Committee for Control and Supervision of Experiments on Animals (CCSEA) and Organisation for Economic Co-operation and Development (OECD) guidelines. Sprague–Dawley rats were acclimated and housed individually under controlled conditions. A polygamous breeding scheme was implemented, and pregnant female rats were assigned to control, vehicle control or treatment group following OECD Test Guideline 414. Lumacaftor and Ivacaftor were administered to pregnant rats at various doses, such as MRHD, 5MRHD, 8MRHD and 10MRHD, from gestation days 6 to 17. Clinical observations, body weight and food consumption of pregnant rats were monitored. Postmortem examinations included caesarean section, reproductive performance (the number of corpora lutea, implantation sites, early and late resorptions and live foetuses) and assessment of foetal analysis. The foetal analysis incorporated external malformation evaluation, visceral examination and skeletal examination using alizarin red solution. Results: In pregnant rats exposed to Lumacaftor and Ivacaftor, the external examination was conducted on 206, 209, 199, 184, 198 and 201 foetuses in their respective groups, each consisting of 19 litters. Within this cohort, approximately 33% of foetuses underwent visceral examination. Additionally, across six groups approximately 50% of foetuses underwent skeletal examination. Importantly, no abnormalities were detected in skeletal, visceral or histopathological assessments across the treatment groups encompassing doses of a combination of Lumacaftor and Ivacaftor at MRHD, 5MRHD, 8MRHD and 10MRHD. Additionally, no significant morbidity or mortality related to the treatment was observed. Conclusion: In conclusion, the study indicates that the combination of Lumacaftor and Ivacaftor at doses equivalent to MRHD, 5MRHD, 8MRHD and 10MRHD did not induce significant teratogenic effects, affirming their safety during pregnancy in rats. [ABSTRACT FROM AUTHOR]

AbstractIn recent years, the presence of pharmaceuticals in the aquatic environment has gained a significant attention. Carbamazepine, a commonly prescribed antiepileptic drug, has been consistently found in aquatic environments at concentrations ranging from nanograms to micrograms, raising concerns about its potential negative impacts on aquatic organisms. The study examined the acute and chronic neurotoxic effects of environmentally relevant and sublethal concentrations of carbamazepine in the mosquitofish Gambusia affinis. After a 96-hour exposure period, the median lethal concentration (LC50) of carbamazepine for G. affinis was determined as 24 mg L − 1. For the current study, sublethal concentrations i.e., one-tenth (2.4 mg L − 1) and one-fifth (4.8 mg L − 1) of the LC50 value were chosen for assessing the neurotoxic effects along with the environmentally relevant concentration (13 ng L − 1). The research findings indicated that carbamazepine had a disruptive impact on the typical growth and behavior of the fish. During the acute exposure phase, physical deformities were observed in the fish, resulting in neonatal and postneonatal fatalities. Furthermore, the neurotoxic effects of carbamazepine were clearly demonstrated through alterations in various neurological parameters, including acetylcholinesterase, dopamine, gamma-aminobutyric acid, serotonin, monoamine oxidase, 5-hydroxyindole acetic acid, adrenaline, and nor-adrenaline. These findings raise concerns about the survival of fish populations in their natural environment. [ABSTRACT FROM AUTHOR]

To assess the risk of major birth defects after first‐trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first‐trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40–1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18–7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients. [ABSTRACT FROM AUTHOR]

Bambusa vulgaris is a commonly consumable plant, which is widely utilized by indigenous peoples as a source of food. Consumption of these plant products in various forms is typically acceptable due to their distinct tastes, and aromatic flavor. However, there is little information on the plant's safety and toxicity profile. Although toxicity information on B. vulgaris is readily available, the impact of plants during pregnancy has yet to be fully explored. To determine the possible mechanism behind teratogenicity, pregnant albino Wistar rats are administered aqueous extracts of B. vulgaris in a dose‐dependent manner. For determining the structural malformations, Teratogenicity indices include maternal common physiological parameters, number of implantations and fetal indices, number of live, resorpsed, and dead somites, morphological malformations, and skeletal malformations of different organs are evaluated by comparing different test groups with control groups. Most developmental indices, including implantation and fetalindices, vertebral, organ, and skeletal structures are significantly altered by the crude extract at higher dosages in treated as compared to control animals. The administration of aqueous extract of B. vulgaris during the organogenesis phase in rats has a considerable deleterious effect on embryonic and fetal developmental indices. It ruthlessly impacts the embryo's numerous organs as well as their typical physiological processes in a dose‐dependent way. The present investigation validates the capacity of B. vulgaris to cause developmental toxicity in Wistar rats, as evidenced by significant alterations in their gestational morphological, structural, and skeletal anatomy and physiology. It is recommended that further scientific studies be conducted to evaluate the more advanced mechanisms of teratogenicity associated with B. vulgaris. [ABSTRACT FROM AUTHOR]

Sodium valproate (SV), as a common anti-epileptic drug, causes teratogenic effects on skeletal system by reactive oxygen species (ROS) generation. Herbal extract of Prosopis Farcta (PF), as a natural antioxidant necessary for many physiological activities, can probably ameliorate the teratogenic effects of SV during pregnancy. This study aimed to investigate the possible anti-teratogenic role of PF and Vitamin E (VE) on skeletal anomalies caused by SV in rat fetuses. Adult female rats (n=30) were categorized into 6 groups including control, SV (400 mg/kg), SV+VE (100mg/kg), and three doses of PF (50, 100, and 150 mg/kg) + SV. Each male rat mated with three adult female rats. The rats received SV, PF and VE at the 8th and 9th days of pregnancy by intraperitoneal injection. The animals were anesthetized and the laparotomy was applied at the 20th day of pregnancy. Skeletal abnormalities were analyzed using Alizarin red and Alcian blue staining. The expression of Runx2 and BMP2 genes was assessed using qPCRTM analysis in limbs bones. SV showed significant teratogenic effects including decrease in the rate of animal weight, Crown-rump length (CRL), various skeletal anomalies. The mRNA expression of Runx2 and BMP2 was also reduced in SV exposed animals. Administration of PF (especially 100mg/kg) in SV-exposed animals increased the weight of animals, CRL index, expression of Runx2 and BMP2, and reduced skeletal anomalies. The body weight, CRL index, Runx2 and BMP2 mRNA expression significantly increased, and skeletal anomalies decreased in VE group compared to the SV group. The results showed that PF could ameliorate the skeletal abnormalities and thus decreased osteogenic associated genes induced by SV in rat offsprings. [ABSTRACT FROM AUTHOR]

Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells. [ABSTRACT FROM AUTHOR]

Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B.

Objective: Many cultures use herbal medicines in pregnancy as a safer treatment than traditional medicine to promote the mother and/or baby health. Horse chestnut, a medicinal herb that mainly contains aescin, is used for its vagotonic impact, vascular protection, and antiedematous properties. This research sought to assess the impact of prenatal administration of horse chestnut extract on fetal development of rats, which is a novel achievement in teratogenesis studies. Methods: Pregnant rats were allocated randomly into four groups. Horse chestnut extract was administered through oral gavage to the animals from day 0 to day 16 of pregnancy at doses of 10, 20, and 40 mg/kg. On day 18, after the cesarean process, the effects of the extract were estimated by morphological, skeletal, and histological studies. Results: Administration of the extract resulted in a substantial decrease in weight, head diameter, tail diameter, and crown-rump length of fetuses. There were no malformations and no lack of toes and legs, and all internal organs of the fetus were completely formed. Also, there was no difference in the overall skeletal opacity and density between the control and treatment groups. Moreover, heart cells and neurons were seen in all the groups but the formation of the central vein, portal area, and hepatic sinusoids were not observed in groups that received the extract. Conclusion: The result of this study revealed that oral administration of horse chestnut extract in pregnant rats could cause teratogenicity. However, some additional clinical studies may be necessary but according to our data, consumption of this herbal extract during pregnancy is not recommended. [ABSTRACT FROM AUTHOR]

Purpose of Review: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA. Recent Findings: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. Summary: While there are multiple safety and tolerability concerns with older regimens, there are now multiple options of regimens that are highly efficacious and have good safety data in pregnancy. Most pregnant patients who are virally suppressed on a well-tolerated regimen are able to safely continue those medications during pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are particles released not only from blood cells but also from various organs. EVs, which are lipid bilayer vesicles, contain proteins, DNAs, and RNAs. The RNA and proteins within EVs display cell-specific characteristics. EVs derived from tumor cells are identified as biomarkers with diagnostic accuracy exceeding 90% for early cancer detection. Furthermore, EV RNA in serum has serves as a biomarker for toxicity. EVs have been found in various body fluids, including saliva, tears, urine, and amniotic fluid. In this study, we aimed to investigate the potential use of EV RNA in amniotic fluid as an indicator of developmental toxicity. Pregnant mice were exposed to valproic acid (VPA), a developmental toxicant, at concentrations of 0, 300, or 600 mg/kg/day on gestational days (GDs) 9-11. The study involved measuring VPA concentration in maternal plasma and fetuses on GD11, fetal weight on GD15 and 18, and assessing external morphological abnormalities on GDs11, 15 and 18. Additionally, EVs were collected from fetal amniotic fluid, and a comprehensive gene expression analysis of EV RNA was conducted on GD15. As a result, the concentration of VPA in the fetuses was not associated with the implantation location. Additionally, the VPA-treated group exhibited intrauterine growth retardation and teratogenic effects, including neural tube defects and digit malformations. EV RNA analysis identified differentially expressed EV small RNAs, both suppressed and induced, in the VPA-treated group compared with the control (vehicle, 0.5% Methylcellulose) group. These findings suggest that EV RNA in amniotic fluid serve as an indicator of developmental toxicity. [ABSTRACT FROM AUTHOR]

Background: Palliative care patients frequently present with clinically significant gastrointestinal bleeding. Due to the existence of confounding comorbidities and a remarkably reduced state of general health in many cases, the management of gastrointestinal bleeding in this population is often challenging. Summary: This review summarizes and discusses the role of thalidomide in gastrointestinal bleeding with a special focus on palliative care patients. In addition, an illustrative case report is presented. Thalidomide may be beneficial in gastrointestinal bleeding by exerting antiangiogenic effects. The drug has an acceptable safety profile. Side effects like neurotoxicity may limit its use but can be monitored safely. Due to thalidomide's thrombin generation potential, patients managed with thalidomide-containing regimes should be closely monitored for deep venous thrombosis. Given its teratogenicity, thalidomide should not be administered to women of childbearing potential who are not using adequate contraception. Key Message: Physicians caring for patients in a palliative care setting should be aware of thalidomide as an effective therapeutic option when endoscopy fails to find a bleeding source or for those patients who cannot or refuse to undergo endoscopy but present with recurrent or obscure gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Abstract Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β‐carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β‐carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child‐bearing age, pregnant and lactating women and post‐menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4–11 months) and 2600 μg RE/day (adolescents 15–17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β‐carotene. The available data were not sufficient and suitable to characterise a dose–response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β‐carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β‐carotene. The use of supplemental β‐carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

Exposure to teratogenic agents during pregnancy can lead to fetal abnormalities. Establishing histological, hematological, and biochemical parameters is pivotal to enhancing the evaluation of the effect of any substance on embryo-fetal development. The present study investigated the maternal toxicity of aqueous extract of Bambusa vulgaris Schrad. ex J.C. Wendl shoots in pregnant Wistar rats. The pregnant rats were then allocated into four groups (n=6): a control group (without treatment) and three test groups (treated with the extract 250, 500, and 1000 mg/Kg, respectively). The treatment was initiated on gestational day (GD) 6 and continued until the 15th day. On GD 20, all the rats were anesthetized and subjected to laparotomy. Blood samples were collected from the pregnant rats for hematological and biochemical analyses, while various organs were isolated for histopathological studies. The study demonstrates dose-dependent toxicity of the extract, with significant variations (P

Context:-Teratogenicity is a major cause of abortion, still birth and can result in longterm disability with a significant impact on individuals, families, societies and healthcare systems. Drugs being one of the causes of teratogenicity, creating awareness among medical students, the future prescribing physicians, the rate of teratogenicity can be decreased. Attainment of right knowledge at right time about teratogenicity of a particular drug is very crucial which requires more awareness among general doctors in a country like India where most of the pregnant females are manged by these doctors only in peripheral regions. Aims:-1. To estimate the knowledge regarding teratogenicity of drugs and their practice of prescribing in pregnant women. 2. To assess the gap between knowledge and practice among the interns. 3. To heighten their awareness and inquisitiveness about teratogenicity of drugs. Settings and Design: This is a descriptive cross-sectional study conducted among interns Methods and Material: The data was collected by self-administered closed ended questionnaire through Google forms. Statistical analysis used: Statistical analysis was performed using SPSS software 21 version. Results: Though majority of interns knew about teratogenic effect of drugs, only 60.8% believed that they can affect fetus through all gestational ages. Good number (73.3%)were practicing preconception counselling also. Conclusions: Based on the findings of present study it is obvious that more emphasis should be put on improving knowledge about teratogenic drugs during early years of medical training in order to bring about necessary changes in existing practices of treating doctors. [ABSTRACT FROM AUTHOR]

Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B. In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the TCOF1 gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity. This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure. [ABSTRACT FROM AUTHOR]

Glutathione is the body's most abundant endogenous non-enzymatic antioxidant and is used as a substrate for free radical scavenging in the body, especially during ethanol metabolism. This study aims to shift the paradigm of using glutathione as a whitening agent into a potent antioxidant for therapy, particularly for ethanol-induced teratogenesis in the Philippines. Zebrafish embryos were treated with glutathione at various time points of ethanol exposure and concentration. Pre-treatments, co-treatments, and post-treatments with 100 µM glutathione solution were done to assess the most appropriate time point for glutathione intake upon exposure of the embryo to ethanol. Eye diameter and otic vesicle diameter were chosen as morphological parameters because dysmorphogenesis of these organs resembles mammalian fetal alcohol syndrome disorders. For eye diameter, alleviation of microphthalmia by glutathione was seen in pre-treatment (1% ethanol only) and post-treatment (1% & 1.5%) while co-treatment did not exhibit rescue for eye diameter reduction. For otic vesicle diameter, pre- and co-treatment with glutathione did not exhibit any changes in size but post-treatment showed abnormal enlargement suggesting possible teratogenic effect across all ethanol concentrations. The 2,2-diphenylpicryl-1-hydrazine (DPPH) assay was used as a confirmatory test for the free radical scavenging activity (FRSA) of treated tissues. Pre-treatment with GSH at 1% ethanol showed the highest FRSA while post-treatment showed FRSA insignificantly different to controls. This study suggests that glutathione can alleviate oxidative stress in embryo development which may lead to dysmorphogenesis and that supplementation before and after ethanol exposure may be a viable form of therapy for ethanol-induced teratogenesis. [ABSTRACT FROM AUTHOR]

Objective: In the absence of safety data in humans, the use of cannabidiol (CBD) is not recommended during pregnancy. Yet >50% of pregnancies in women with epilepsy are unintended, making fetal exposure to CBD possible. As a small‐molecule, highly lipid‐soluble drug, CBD is likely to be distributed into the placenta and cross it. To estimate the placental distribution profile of CBD and its potential short‐term placental effects, we conducted an ex vivo perfusion study in human placentas. Methods: Placentas were obtained from healthy women undergoing cesarean deliveries. Selected cotyledons were cannulated and perfused for 180 min with a CBD‐containing medium (250 ng/mL,.796 μmol·L−1; representative of a low therapeutic concentration; n = 8). CBD concentrations were determined at 180 min in the medium and placental tissue using liquid chromatography–tandem mass spectrometry. A customized gene panel array was used to analyze the expression of selected genes in the perfused placental cotyledons as well as in placentas perfused with 1000 ng/mL CBD (3.18 μmol·L−1; high therapeutic concentration; n = 8) and in those exposed to the vehicle. Results: CBD was sequestered in the placental tissue, exhibiting significant variability across samples (median = 5342 ng/g tissue, range = 1066–9351 ng/g tissue). CBD concentrations in the fetal compartment were one fifth of those measured in the maternal compartment (median = 59 ng/mL, range = 48–72 ng/mL vs. 280 = ng/mL, range = 159–388 ng/mL, respectively; p <.01). Placental gene expression was not significantly altered by CBD. Significance: The placenta acts as a depot compartment for CBD, slowing down its distribution to the fetus. This phenomenon might yield flatter but prolonged fetal CBD levels in vivo. The attenuated transplacental CBD transfer does not imply that its use by pregnant women is safe for the fetus. Only pregnancy registries and neurocognitive assessments would establish the risk of being antenatally exposed to CBD. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) has a rich history spanning thousands of years, with its applications ranging from treating female infertility and recurrent pregnancy loss to managing nausea and vomiting of pregnancy. Yet the safety of pregnant women consuming Chinese herbal medicine (CHM) still lacks sufficient modern clinical research data. On April 19, the journal Acta Obstetricia et Gynecologica Scandinavica published a research article titled "Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study." The study claimed that "Periconceptional TCM exposure is associated with an increased risk of congenital malformation," drawing attention from both English and Chinese media outlets, which extensively reported and commented on the findings. In response, various TCM organizations contested the research, asserting that it failed to adhere to fundamental standards of academic rigor, statistical analysis, and necessary methodologies to draw conclusions. International TCM practitioners and scholars thoroughly examined the article, uncovering multiple errors and arguing that these misleading conclusions significantly undermined the reputation of CHM. These scholars communicated their doubts directly to the corresponding author and the journal's chief editor, emphasizing that the article's conclusion was derived from secondary data analysis of another clinical research project and funding sources, therefore, called for withdrawal of the article. Eventually, the article was retracted due to flaws with the study design in collecting data on exposure to TCM in pregnant women, which affects the validity of the data to support the conclusions of the study. This article conducts a comprehensive academic inquiry into the article, meticulously outlining the identified errors, discusses the reproductive toxicity of CHM, and provides suggestions for future research to evaluate the safety of pregnant women using CHM rigorously, emphasizing evaluation on teratogenicity research of CHM should not only be based on study using healthy animals, but also incorporate clinical epidemiological research and disease-syndrome-based toxicology. [ABSTRACT FROM AUTHOR]

Herbal medicines are increasingly being used during pregnancy and little is known of their potential teratogenic effect. The present study is therefore designed to investigate the teratogenic effects of methanol extracts ofthree medicinal plants; Jatropha curcas, Alchornea cordifolia, and Secamone afzelii in Wistar rats. The animals were administered the extractsat doses of 50, 100, and 200 mg/kg.Morphometry of the placenta and foetus were recorded, the weight, crownrump length, head circumference and anogenital distance were measured. Acute toxicity of the extracts was also evaluated. Embryo resorptions in some treated rats as well as foetal malformation were observed. In the acute toxicity test, at the maximum dose of 5000 mg/kg, the methanol extracts of the three plants; Jatropha curcas, Alchornea cordifolia, and Secamone afzelii showed no harmful effects on the pregnant rats. However, strong teratogenic effects were noted. At doses higher than 50mg/kg, Alchornea cordifolia extract-exposed pregnant rats produced 7 dead foetuses out of 9 implantations; the live foetuses were deformed, particularly in their limbs. Animals administered with Secamone afzelii had 11% foetal mortality at 100 and 200mg/kg dose. No dead foetus or foetal deformity wasobserved in the rats administered with 50, 100, and 200 mg/kg Jatropha curcasextract. Although the methanolextracts of the plants used in this study were not acutely toxic to pregnant Wistar rats at the doses tested, they caused some teratogenic effects, especially with Alchornea cordifolia extracts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A novel series of triazole-quinazoline hybrid molecules was synthesized and characterized by spectral analyses. The H37 RV strain was used to test the newly synthesised compounds for antitubercular efficacy against Mycobacterium tuberculosis. Some of the synthesized compounds were effective compared with standard pyrazinamide at a concentration of 3.12 μg/mL. Additionally, molecular docking investigations were conducted on all synthesized compounds against the M. tuberculosis InhA protein, which is attenuated by the PT70 X-ray crystal structure, PDB ID: 2X22. Two compounds were revealed the best against 2X22, with Autodock scores of –9.13 and –8.59, respectively. To further investigate the teratogenicity of the synthesized compounds, zebrafish larvae were employed. At a concentration of 100 μM, some compounds showed no signs of abnormality. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the risk of congenital malformation among pregnant women exposed to the mRNA COVID-19 vaccines during the first trimester of pregnancy, which is a developmental period where the foetus is at risk of teratogenicity. Pregnant women were prospectively enrolled from March 2021 to March 2022, at the time of COVID-19 vaccination. Pregnant women exposed to at least one dose of mRNA COVID-19 vaccine from conception to 11 weeks of gestations and 6 days were compared with pregnant women exposed to the vaccine from 12 weeks to the end of pregnancy. The primary outcome was a confirmed congenital malformation at birth. A total of 1450 pregnant women were enrolled including 124 in the first trimester and 1326 in the second and third trimester. The overall proportion of congenital malformation was 0.81% (n = 1/124; 95% CI: 0.02–4.41) and 0.83% (n = 11/1326; 95% CI: 0.41–1.48) among pregnant exposed to the COVID-19 vaccine during the first and second/third trimester, respectively. First trimester exposure was not associated with a higher risk of congenital malformation with a relative risk of 0.89 (95% CI: 0.12–6.80) with no significant changes after adjustment through exploratory analysis. Pregnant women exposed to mRNA COVID-19 vaccine before 12 weeks of gestation did not have an increased risk of congenital malformation compared with women exposed outside the teratogenic window. Because vaccination is safe and effective, emphasis must be placed on promoting vaccination during pregnancy. [ABSTRACT FROM AUTHOR]

Psychedelic use is rapidly growing in popularity for recreational and clinical purposes, but its potential risks for pregnant and breastfeeding women are currently unknown. The teratogenic potential of psychedelics was notably last considered in the 1970s and little attention has been given to this topic since the recent re-emergence of the field. Human case studies and previous animal studies provide mixed findings and we propose the zebrafish for the safety profiling of fetal psychedelic exposure. Practical simplicity, translational relevance, and established laboratory techniques make the zebrafish an effective animal model for fetal exposure studies Psychedelic drugs have experienced an unprecedented surge in recreational use within the past few years. Among recreational users, the risks of psychedelic use by pregnant and breastfeeding women are severely understudied and there is little information on the potential teratogenic effects of these drugs. We provide an overview of the previous data on psychedelic teratogenicity from rodent studies and human surveys, discuss their limitations, and propose the utility of the zebrafish as a potential effective model for investigating psychedelic teratogenicity. Recent years have validated the use of zebrafish in the study of fetal exposure and developmental biology; we highlight these properties of the zebrafish for its suitability in psychedelic toxicity research. [ABSTRACT FROM AUTHOR]

Abstract Background There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong. Methods This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics. Results Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics. Conclusion We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.

Objective: There is limited safety data on the use of everolimus during pregnancy. In this study, we present the maternal and neonatal outcomes of everolimus used throughout the course of pregnancy and conducted a systematic review of reports of everolimus use after organ transplantation during pregnancy. Case report: A woman with type 1 diabetes who underwent kidney transplantation was treated with tacrolimus, everolimus, and prednisolone. Two years later, she became pregnant. At 27 weeks of gestation, an emergent cesarean delivery was performed owing to severe preeclampsia and fetal distress. No congenital malformation was noted in the baby at a corrected age of 4 months, and the maternal renal function remained stable. Conclusion: Our systematic review did not identify evidence of teratogenicity in babies exposed to everolimus as an immunosuppressant after transplantation. To better assess the risk of exposure to everolimus during pregnancy, all cases of new pregnancies occurring in transplant recipients receiving treatment with mammalian target of rapamycin inhibitor inhibitors should be reported.

The incidence of coronavirus disease (COVID-19) is increasing each day worldwide and the clinico-pharmacological dynamics of it is also changing with time. Pregnant women do also get infected though mostly mild to moderate in nature. To date, there is no specific drug against the severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2), more so its drug management in pregnancy in view of adverse maternal and fetal effects. There are different treatment modalities described in literature. Here, we present a case of severe COVID-19 pneumonia in second trimester pregnancy managed successfully with “off label” use of tofacitinib along with steroid pulse therapy in preventing her from going to invasive mechanical ventilation and probable catastrophe due to hyperinflammatory syndrome characterised by surge of cytokines.

Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells.

Background & aimsWe conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes.MethodsUsing a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607).ResultsAs compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads.ConclusionsIn a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

Background. The increase in infectious and non-infectious diseases occurrence during pregnancy prompts scientists to search for substances that can fight these ailments. This especially applies to natural substances that have virtually no side effects. These include substances obtained from medicinal leeches. These substances have a wide range of therapeutic effects; as to their practical use, all preclinical studies must be completed. This particularly refers to the presence of an embryotoxic effect. The aim of this work was to investigate the effect of the water-salt extract of the medicinal leech Hirudo verbana Carena, 1820 on the general course of embryogenesis in rats when administered intraperitoneally. Materials and Methods. The work was performed on female non-linear white rats. Two experimental groups of animals were injected intraperitoneally with a water-salt extract of the medicinal leech at a concentration of 5 μg/g of the animal, in a volume of 0.5 mL, three times before mating and three times during pregnancy every 3 days. Two control groups were injected intraperitoneally with physiological saline according to the same scheme as the experimental groups. Subsequently, one of the control and experimental groups underwent euthanasia, dissection of the abdominal cavity and uterine horns on the 20th day of pregnancy. We analyzed the total number of corpora lutea of pregnancy, the number of live and dead fetuses. Fetuses were weighed, examined for the presence of skin hematomas, mutilations, and external abnormalities in the develop­ment of internal organs. The other two groups of control and experimental animals were left until the offspring were born. Then the females of both groups were weighed, and their general condition was assessed. Newborn rats were examined, weight and body length were determined, mortality was recorded from the beginning of birth to 15 days, the presence of skin hematomas, mutilations, and external anomalies of the development of internal organs were checked. Results and discussion. The study established that the intraperitoneal injection of a water-salt extract of a medicinal leech before and during pregnancy in female rats does not cause any toxic effect during embryogenesis and at the early stages of post-embryonic ontogenesis. During the external examination of fetuses and offspring in both groups, no developmental anomalies were noted, all organs in both groups were of normal topography and size. The number of subcutaneous hematomas in the experimental group of fetuses compared to the control group decreased by an average of 50%, postnatal mortality decreased by an average of more than 3 times, as well as an increase in body weight in females, an increase in body weight and body length in the fetus and offspring in the early post-embryonic period ontogenesis (p

Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was to investigate the embryotoxic, foetotoxic, and teratogenic effects of thiozonide in pregnant rabbits.Materials and methods. The study involved 66 pregnant rabbits (4 groups of 16–17 animals each). The rabbits received oral thiozonide from day 6 to day 19 of gestation at doses of 20.6 mg/kg (1 TD (therapeutic dose)), 103 mg/kg (5 TDs), and 206 mg/kg (10 TDs). The control group received a 1% starch solution. The authors conducted a macroscopic examination of the reproductive organs and a histological evaluation of the placenta in eutha nised pregnant rabbits. Live foetuses underwent a check for developmental abnormalities, a skeletal development evaluation with a modified Dawson’s method, and a histologic examination of the internal organs.Results. The study showed no clinical signs of toxicity and no mortality associated with thiozonide in pregnant rabbits across all dose groups. Macroscopic and histological examinations revealed no pathological changes in the reproductive organs of pregnant rabbits. The evaluation of embryotoxic and foetotoxic effects did not identify any differences between the foetuses of the animals assigned to different doses of thiozonide and the control group. The authors found no developmental abnormalities in the foetuses. Examinations of foetal skeleton development and internal organ condition identified no differences between the groups and no abnormalities. The authors registered the death of all foetuses (late resorption) in one rabbit from the 206 mg/kg group. Therefore, the 103 mg/kg dose (5 TDs) was selected as a reasonable No Observed Adverse Effect Level (NOAEL).Conclusions. Thiozonide has no embryotoxic, foetotoxic, or teratogenic effects.

Mycotoxins are fungal products often found in food, formed during growth, harvesting, drying or storage of fruits, seeds, or grains, leading to a variety of toxic effects in humans and animals. Aflatoxins are a family of polyketide secondary metabolite produced by the food-contaminating moulds Aspergillus parasiticus and Aspergillus flavus. Aflatoxin B1 (AFB1) is a carcinogenic, teratogenic, mutagenic and growth inhibitory mycotoxin. To explore the negative morphological effects of AFB1 on the developing mice embryo, 50 adult females albino mice (CD1) were divided into five groups (10 females for each group): Control, positive control and three groups treated with a daily oral dose of 5, 10 or 20 μg/kg bw of AFB1 extract. Fifteen days after treatments, females were caged with males. Pregnancy, mortality, embryos number rates and body weight of female mice and infants were recorded. At 21 days old, crown rump, head, ear, tail, fore and hind-limb lengths of mice infants were investigated. Current data showed a decrease in pregnancy and embryo number rate among females in the animals treated with 10 & 20 μg AFB1, while treatment with 5 μg showed an increase in pregnancy and embryo number rate compared to control one, while mortality rate among fetuses increased in the three experimental animals treated with AFB1. Some cases of abortion were observed in 10 & 20 μg groups, while ulcers were observed in 20 μg groups. Weight and all morphometric parameters showed significant decrease except tail length that showed insignificant increase in the treated groups compared to the control one, while ear length showed significant increase. Different congenital malformations were observed in infants such as tail loss, delayed hair and teeth development and poor ossification in treated groups. The present study demonstrated that AFB1 induced developmental anomalies and reduced quality and birth rate. Data clarified that minimum concentration of AFB1 required to induce teratogenicity is far beyond the minimum concentrations estimated in earlier literatures. It is suggested that AFB1 might change genetic elements and consequently interfere with bone mineralization and induce teratogenicity and anomalies during mice embryonic development. Further studies are required to explore the mechanism of action.