Browsing by Author "Magnin, Geraldine"
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- Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in RodentsHrubec, Terry C.; Melin, Vanessa E.; Shea, Caroline S.; Ferguson, Elizabeth E.; Garofola, Craig; Repine, Claire M.; Chapman, Tyler W.; Patel, Hiral R.; Razvi, Reza M.; Sugrue, Jesse E.; Potineni, Haritha; Magnin, Geraldine; Hunt, Patricia A. (2017-08-15)Background: Quaternary ammonium compounds are a large class of chemicals used for their antimicrobial and antistatic properties. Two common quaternary ammonium compounds, alkyldimethylbenzyl ammonium chloride (ADBAC) and didecyldimethyl ammonium chloride (DDAC), are combined in common cleaners and disinfectants. Introduction of a cleaner containing ADBAC+DDAC in the vivarium caused neural tube defects (NTDs) in mice and rats. Methods: To further evaluate this finding, male and female mice were dosed in the feed at 60 or 120 mg/kg/day, or by oral gavage at 7.5, 15, or 30 mg/kg ADBAC+DDAC. Mice also received ambient exposure to ADBAC+DDAC from the disinfectant used in the mouse room. Embryos were evaluated on gestational day 10 for NTDs, and fetuses were evaluated on gestational day 18 for gross and skeletal malformations. Results: We found increased NTDs with exposure to ADBAC+DDAC in both rats and mice. The NTDs persisted for two generations after cessation of exposure. Notably, male exposure alone was sufficient to cause NTDs. Equally significant, ambient exposure from disinfectant use in the vivarium, influenced the levels of NTDs to a greater extent than oral dosing. No gross or significant axial skeletal malformations were observed in late gestation fetuses. Placental abnormalities and late gestation fetal deaths were increased at 120 mg/kg/day, which might explain the lack of malformations observed in late gestation fetuses. Conclusion: These results demonstrate that ADBAC+DDAC in combination are teratogenic to rodents. Given the increased use of these disinfectants, further evaluation of their safety in humans and their contribution to health and disease is essential. (C) 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.
- Comparative Pharmacokinetics and Tissue Concentrations of Flunixin Meglumine and Meloxicam in Tilapia (Oreochromis spp.)Martin, Miriam; Smith, Stephen A.; Kleinhenz, Michael; Magnin, Geraldine; Lin, Zhoumeng; Kuhn, David; Montgomery, Shawnee; Coetzee, Johann (MDPI, 2021-11-25)Evidence of pain perception in fish is well established, but analgesic use in aquaculture is limited. The objective was to investigate the comparative pharmacokinetics of flunixin administered intramuscularly (IM) and meloxicam administered IM or orally (PO) in tilapia. Two hundred and seventy fish were assigned to 1 of 3 treatment groups: flunixin meglumine IM (2.2 mg/kg); meloxicam IM (1 mg/kg); or meloxicam PO (1 mg/kg). Blood and tissue samples were collected from 6 fish per treatment at 14 time points for 10 days. Drug concentrations were determined using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Plasma concentration versus time data were analyzed with a non-compartmental approach using a commercially available software. Flunixin reached a mean maximum concentration (Cmax) of 4826.7 ng/mL at 0.5 h, had a terminal half-life (T1/2) of 7.34 h, and an area under the concentration–time curve extrapolated to infinity (AUCINF_obs) of 25,261.62 h·ng/mL. Meloxicam IM had a T1/2 of 9.4 h after reaching a Cmax of 11.3 ng/mL at 2 h, with an AUCINF_obs of 150.31 h·ng/mL. Meloxicam PO had a T1/2 of 1.9 h after reaching a Cmax of 72.2 ng/mL at 2 h, with an AUCINF_obs of 400.83 h·ng/mL. Tissue concentrations of both drugs were undetectable by 9 h. Flunixin reached a sufficient plasma concentration to potentially have an analgesic effect, while meloxicam, when administered at the given dosage, likely would not.
- Studies Exploring the Interaction of the Organophosphorus Compound Paraoxon with FullerenesMagnin, Geraldine; Bissel, Philippe; Council-Troche, Roberto McAlister; Zhou, Zhiguo; Ehrich, Marion F. (2019-11-12)In vitro experiments previously published demonstrated the ability of fullerenes to decrease the capability of organophosphorus (OP) compounds to inhibit acetylcholinesterase. Experiments described herein demonstrate molecular level affinity interactions between fullerenes and the OP test compound paraoxon with NMR spectroscopy. The calculated binding constant of 19 M-1 indicates that this binding was not covalent.