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Developmental Toxicity

Yassine Ait-Bali, Saadia Ba-M'hamed, Mohammed Bennis
In the present work, we investigated developmental toxicity of Paraquat (PQ), from the 1st or 6th day of mating and throughout the gestation period. We have examined several parameters, including toxicity indices, reproductive performance, sensorimotor development, as well as anxiety and cognitive performance of the offspring. Our results showed that exposure to 20mg/kg of Paraquat during the first days of pregnancy completely prevents pregnancy in treated mice, but from the 6th day of pregnancy, an alteration in fertility and reproductive parameters was observed...
October 13, 2016: Environmental Toxicology and Pharmacology
Bénazir Siddeek, Nadjem Lakhdari, Lilia Inoubli, Rachel Paul-Bellon, Véronique Isnard, Emmanuelle Thibault, André Bongain, Daniel Chevalier, Emanuela Repetto, Michele Trabucchi, Jean-François Michiels, Catherine Yzydorczyk, Umberto Simeoni, Michel Urtizberea, Claire Mauduit, Mohamed Benahmed
AIM: The Developmental Origin of Health and Disease refers to the concept that early exposure to toxicants or nutritional imbalances during perinatal life induces changes that enhance the risk of developing noncommunicable diseases in adulthood. Patients/materials & methods: An experimental model with an adult chronic germ cell phenotype resulting from exposure to a xenoestrogen was used. RESULTS: A reciprocal negative feedback loop involving decreased EZH2 protein level and increased miR-101 expression was identified...
October 20, 2016: Epigenomics
Lisa M Sweeney, Michael L Gargas
To help develop a comprehensive, quantitative understanding of the hazards of 1,2-dichloroethane (ethylene dichloride, EDC, CAS No. 107-06-2) exposure by the inhalation route, the results of existing subchronic studies and an extended one-generation reproductive toxicity (EOGRT) study recently conducted by the oral route in rats were extrapolated using a physiologically based pharmacokinetic (PBPK) model. The no observed adverse effects levels (NOAELs) for the endpoints of neurotoxicity and reproductive/developmental toxicity were the highest tested doses of 169 and 155 mg/kg-day, respectively...
October 15, 2016: Regulatory Toxicology and Pharmacology: RTP
Emily May Lent, Lee C B Crouse, Allison M Jackovitz, Erica E Carroll, Mark S Johnson
Nitrotriazolone (1,2,4-triazol-5-one; NTO), an insensitive, energetic material used in explosive formulations, induced testicular toxicity and oligospermia in repeated-dose oral toxicity tests in rats. To evaluate whether NTO produces additional reproductive and developmental effects, a modified extended one-generation reproductive toxicity test was conducted. Rats were provided ad libitum access to NTO in drinking water at 0-, 144-, 720-, or 3600-mg/L NTO. Treatment of the parental generation began 2 (females) and 4 (males) wk premating and continued until weaning of litters...
October 18, 2016: Journal of Toxicology and Environmental Health. Part A
Justin D Vidal
Evaluation of the female reproductive system in a general toxicity setting can be challenging for the toxicologic pathologist due to the cyclic nature of the estrous and menstrual cycles, timing of puberty and reproductive senescence, and species differences. Age in particular can have a significant impact on the histologic appearance of the female reproductive system and create challenges when trying to distinguish test article-related findings from normal developmental or senescent changes. This review describes the key physiologic and histologic features of immaturity, the transition through puberty, sexual maturity, and reproductive senescence in the female reproductive system, with an emphasis on practical applications for the toxicologic pathologist, and includes recommendations for distinguishing and documenting these developmental periods...
October 17, 2016: Toxicologic Pathology
Ying Peng, Pu Xia, Junjiang Zhang, Daniel L Villeneuve, Jiamin Zhang, Zhihao Wang, Si Wei, Hongxia Yu, Xiaowei Zhang
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are analogs of PBDEs with hundreds of possible structures and are frequently detected in the environment. However, the in vivo evidence on the toxicity of OH-PBDEs is still very limited. Here the developmental toxicity of 6-OH-BDE47, a predominant congener of OH-PBDEs detected in the environment, in chicken embryos was assessed using a toxicogenomic approach. Fertilized chicken eggs were dosed via in ovo administration of 0.006 to 0.474 nmol 6-OH-BDE47/g egg followed by 18-days incubation...
October 17, 2016: Environmental Science & Technology
Daniel Hanna, Ariane Emami Riedmaier, Kim S Sugamori, Denis M Grant
The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development...
October 13, 2016: Toxicology
Brigham J Hartley, Kristen J Brennand
Human induced pluripotent stem cells (hiPSCs) can theoretically yield limitless supplies of cells fated to any cell type that comprise the human organism, making them a new tool by which to potentially overcome caveats in current biomedical research. In vitro derivation of central nervous system (CNS) cell types has the potential to provide material for drug discovery and validation, safety and toxicity assays, cell replacement therapy and the elucidation of previously unknown disease mechanisms. However, current two-dimensional (2D) CNS differentiation protocols do not faithfully recapitulate the spatial organization of heterogeneous tissue, nor the cell-cell interactions, cell-extracellular matrix interactions, or specific physiological functions generated within complex tissue such as the brain...
October 12, 2016: Neurochemistry International
Madhuri A Inupakutika, Soham Sengupta, Amith R Devireddy, Rajeev K Azad, Ron Mittler
Reactive oxygen species (ROS) play a key role in the regulation of many biological processes in plants. Nonetheless, they are considered highly reactive and toxic to cells. Owing to their toxicity, as well as their important role in signaling, the level of ROS in cells needs to be tightly regulated. The ROS gene network, encoding a highly redundant arsenal of ROS scavenging mechanisms and an array of enzymes involved in ROS production, regulates ROS metabolism and signaling in plants. In this article, we review the role of the ROS gene network in plants and examine how it evolved...
October 14, 2016: Journal of Experimental Botany
Guozhu Ye, Yajie Chen, Hong-Ou Wang, Ting Ye, Yi Lin, Qiansheng Huang, Yulang Chi, Sijun Dong
Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA...
October 13, 2016: Scientific Reports
Rachana Singh, Samiksha Singh, Parul Parihar, Rohit K Mishra, Durgesh K Tripathi, Vijay P Singh, Devendra K Chauhan, Sheo M Prasad
Reactive oxygen species (ROS) are generated inevitably in the redox reactions of plants, including respiration and photosynthesis. In earlier studies, ROS were considered as toxic by-products of aerobic pathways of the metabolism. But in recent years, concept about ROS has changed because they also participate in developmental processes of plants by acting as signaling molecules. In plants, ROS regulate many developmental processes such as cell proliferation and differentiation, programmed cell death, seed germination, gravitropism, root hair growth and pollen tube development, senescence, etc...
2016: Frontiers in Plant Science
Daniele Mandrioli, Fiorella Belpoggi, Ellen K Silbergeld, Melissa J Perry
Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells...
October 12, 2016: Environmental Health: a Global Access Science Source
Bryson E Finch, Emily S Stefansson, Chris J Langdon, Suzanne M Pargee, Susanna M Blunt, Susan J Gage, William A Stubblefield
Polycyclic aromatic hydrocarbons (PAHs) have been reported to absorb ultraviolet (UV) light, resulting in enhanced toxicity. Early developmental stages of bivalves may be particularly susceptible to photo-enhanced toxicity during oil spills. In the current study, toxicity tests were conducted with sperm and three larval ages of the eastern oyster (Crassostrea virginica) to evaluate the photo-enhanced toxicity of low-energy water-accommodated fractions (WAFs) of two weathered Macondo crude oils collected from the Deepwater Horizon incident...
October 7, 2016: Marine Pollution Bulletin
Kanae Karita, Mineshi Sakamoto, Minoru Yoshida, Nozomi Tatsuta, Kunihiko Nakai, Miyuki Iwai-Shimada, Toyoto Iwata, Eri Maeda, Kozue Yaginuma-Sakurai, Hiroshi Satoh, Katsuyuki Murata
More than sixty years has passed since the outbreak of Minamata disease, and high-level methylmercury contaminations now seem nonexistent in Japan. However, mercury has been continuously discharged from natural sources and industrial activities, and the health effects on children susceptible to methylmercury exposure at low levels, in addition to mercury contamination from mercury or gold mining areas in developing countries, become a worldwide concern. In this article, we provide a recent overview of epidemiological studies regarding methylmercury and mercury...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Sara Mostafalou, Mohammad Abdollahi
Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity...
October 8, 2016: Archives of Toxicology
Dalin Shi, Dongmei Lv, Wanxin Liu, Rong Shen, Dongmei Li, Haizheng Hong
The brominated flame retardants hexabromocyclododecanes (HBCDs) are ubiquitous environmental contaminants, widely distributed in aquatic systems including the marine environment and marine organisms. HBCDs are toxic to the development of both freshwater and marine fish. However, the impacts of HBCDs on marine invertebrates are not well known. In this study, the marine copepod, Tigriopus japonicus, was used to assess the bioaccumulation and developmental toxicity of technical HBCD (tHBCD) through water-borne exposure...
October 5, 2016: Chemosphere
Larissa M Williams, Briony A Lago, Andrew G McArthur, Amogelang R Raphenya, Nicholas Pray, Nabil Saleem, Sophia Salas, Katherine Paulson, Roshni S Mangar, Yang Liu, Andy H Vo, Jordan A Shavit
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants as compared to an adult. In response to pro-oxidant exposure, members of the Cap'n'Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs) activate the expression of genes whose protein products contribute to reduced toxicity. Here, we studied the role of the CNC protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish (Danio rerio)...
October 1, 2016: Aquatic Toxicology
Mohammad Charehsaz, Karin Sørig Hougaard, Hande Sipahi, Asiye Işın Doğan Ekici, Çiğdem Kaspar, Mustafa Culha, Ülkü Ündeğer Bucurgat, Ahmet Aydin
BACKGROUND: Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms indicate some adverse effects on living organisms, but little is known about their potential for developmental toxicity. In this study, developmental toxicity of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were investigated in rats. METHODS: Animals were dosed by gavage from gestation day 7 - 20. The day after parturition, dams and pups were sacrificed and Ag level assessed in several maternal and pup organs...
October 6, 2016: Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
Scott D Wagner, Tomofumi Kurobe, Bruce G Hammock, Chelsea H Lam, Gary Wu, Natalia Vasylieva, Shirley J Gee, Bruce D Hammock, Swee J Teh
Pesticides in urban runoff are a major source of pollutants in aquatic ecosystems. Fipronil, a phenylpyrazole insecticide, found in structural pest control products, turf grass control, and home pet flea medication, has recently increased in use and is commonly detected in urban runoff. However, little is known about the effects of fipronil on aquatic organisms at early developmental stages. Here, we evaluated toxicity of fipronil to embryos of Japanese Medaka (Oryzias latipes, Qurt strain) using a high-throughput 96-well plate toxicity test...
January 2017: Chemosphere
Paul M D Foster
Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning...
October 5, 2016: Toxicologic Pathology
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