Environmental Exposures and Reproduction *
Michele Kiely in Reproductive and Perinatal Epidemiology, 2019
The fields of developmental and reproductive toxicology have undergone great growth in the years since 1961 when thalidomide was first identified as a developmental toxicant. In the early years, teratogens (i.e., agents that cause structural malformations in offspring exposed during critical developmental times) were of primary concern. More recently, the term “teratology” has been replaced with the more broadly defined term, “developmental toxicology”: “the study of adverse effects on the developing organism that may result from exposure prior to conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism. The major manifestations of developmental toxicity include: (1) death of the developing organism, (2) structural abnormality, (3) altered growth, and (4) functional deficiency.”4
Testing for Reproductive Hazards from Dermal Exposure
Francis N. Marzulli, Howard I. Maibach in Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
Short-term and long-term animal-model tests are available for determining reproductive effects. Developmental toxicity tests, i.e., short-term tests, are used to ascertain the effects of a substance on a developing fetus; the test compound is administered to pregnant animals at least from implantation to the end of gestation. Shortly before the expected date of delivery, the animals are terminated, the uterine contents are examined, and the fetuses are evaluated for visceral and skeletal development. In long-term tests, the test substance is administered, and the effects on reproduction and fertility are observed during several generations. In such multigeneration reproduction and fertility studies, the test substance is administered to the animals prior to the first mating, and throughout the experiment during the resulting pregnancies, to the final weaning of the offspring several generations later.
Reproductive and Developmental Toxicity Studies by Cutaneous Administration
Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach in Health Risk Assessment, 2017
One of the major potential confounders in the developmental toxicity study is that any developmental toxicity observed may be due to the systemic maternal toxicity per se, which is required at the top dose by current governmental testing guidelines. That is, the adverse embryo/fetal findings may be due, at least in large part, to the compromised physiological status of the maternal animal and not due to any direct action of the test agent, if the developmental and maternal effects are observed at the same dose(s). A recent discussion8 suggests that developmental toxicity produced at maternally toxic doses should not be ignored if the developmental effects occur as fairly specific types or syndromes and/or if human exposures may occur at toxic levels (e.g., smoking, alcohol, solvents, etc.).
In silico evaluation of multispecies toxicity of natural compounds
Published in Drug and Chemical Toxicology, 2021
Sripriya N., Ranjith Kumar M., Ashwin Karthick N., Bhuvaneswari S., Udaya Prakash N. K.
Bioaccumulation factor is the ratio of the concentration of a chemical in fish due to absorption via the respiratory surface with respect to water at steady state. In general, a compound is termed bioaccummulative, if its BF value is greater than 2000 and very bioaccummulative if its value is greater than 5000 (Burden et al. 2014). In the present study, the bioaccumulation factor for all the compounds was less than 2000, and hence, non-bioaccummulative in nature. Developmental toxicity defines whether a particular chemical causes any effect that hinders normal development, both before and after birth. Most of the compounds i.e., 15 out of 27 studied from the plants – C. angustifolium, C. carandas, and E. oxypetalum were developmental toxicants. Compounds that are positive to Ames mutagenicity test are regarded as potential carcinogens (Griffiths et al. 2000). The non-mutagenicity of the 27 compounds studied, except for Dasycarpidan-1-methanol, acetate (ester), suggests that the compounds can be explored in different industries.
Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-β-boswellic acid (AKBA) through oxidative stress
Published in Drug and Chemical Toxicology, 2022
Liwen Han, Qing Xia, Lei Zhang, Xuanming Zhang, Xiaobin Li, Shanshan Zhang, Lizhen Wang, Changxiao Liu, Kechun Liu
The developmental toxicity assay was performed as previously described (Xia et al. 2017). In brief, normal embryos at 4 hpf were selected under a SZX16 stereo microscope (Olympus, Tokyo, Japan) and randomly transferred to preconditioned 24-well plates (10 embryos per well) (Corning, New York, USA) refilled with either exposure solutions or fish water to reach a final volume of 2 mL per well. A pre-experiment was performed to determine none lethal and total lethal concentrations. Finally, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 μM of AKBA were selected as the exposure concentrations to establish a lethality curve. The mortality of zebrafish embryos was recorded at 24, 48, 72 and 96 hpf. Morphological abnormalities in development were examined at 24, 48, 72 and 96 hpf. Hatching rate at 72 and 96 hpf was recorded. The body length at 96 hpf was measured using Image-Pro Plus (Media Cybernetics, Bethesda, USA).
In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish
Published in Journal of Immunotoxicology, 2020
Drake W. Phelps, Ashley A. Fletcher, Ivan Rodriguez-Nunez, Michele R. Balik-Meisner, Debra A. Tokarz, David M. Reif, Dori R. Germolec, Jeffrey A. Yoder
The initial goal of this project was to investigate if exposure to nonteratogenic levels of twelve structurally diverse chemicals (Figure 1) impacted ROS production in zebrafish embryos. To identify exposure levels at which embryos were viable and lacked identifiable morphological malformations, an initial range-finding study to determine a NOEL for developmental toxicity was performed. Embryos were exposed to various doses (8.80 nM to 80.0 μM) of each chemical, beginning at 6 hpf. Daily media changes were performed until 96 hpf upon which gross morphological assessment was performed via dissecting light microscope (Figure 2(A)). Among the xenobiotics, the NOEL for developmental toxicity varied (Figure 2(B)). Of the 12 tested compounds, five (azathioprine, dexamethasone, dichloroacetic acid, lead acetate, and trichloroethylene) had no adverse effects in the developmental toxicity assay. For these compounds in this assay, the NOEL was determined to be 80 μM. The remaining seven agents had varying potencies ranging from 27.5 nM to 8.19 μM (Figure 2(B)). The most potent xenobiotic identified in this assay was hydroquinone.
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