Article
Medicine, Legal
Honesty Tohon, Mathieu Valcke, Rocio Aranda-Rodriguez, Andy Nong, Sami Haddad
Summary: This study used a reverse dosimetry PBPK modeling approach to estimate toluene atmospheric exposure from urinary measurements of S-benzylmercapturic acid. Results showed that estimating toluene exposure based on spot measurements generated more variability and uncertainty compared to 24-h urine samples. Toluene levels estimated were well below Health Canada's maximum chronic air guidelines, suggesting low health risks.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Toxicology
Andrea Rowan-Carroll, Anthony Reardon, Karen Leingartner, Remi Gagne, Andrew Williams, Matthew J. Meier, Byron Kuo, Julie Bourdon-Lacombe, Ivy Moffat, Richard Carrier, Andy Nong, Luigi Lorusso, Stephen S. Ferguson, Ella Atlas, Carole Yauk
Summary: This study focused on four model PFAS and found that they may have common molecular targets and toxicities, with PFOS and PFDS being the most similar. The data from the study provide baseline toxicity levels for comparison with other known PFAS.
TOXICOLOGICAL SCIENCES
(2021)
Review
Environmental Sciences
Melvin E. Andersen, Pankajini Mallick, Harvey J. Clewell III, Miyoung Yoon, Geary W. Olsen, Matthew P. Longnecker
Summary: The translation discusses the assessment of biomarkers in human populations and the issue of PK bias, emphasizing the factors that need to be considered when studying health effects at low levels of exposure.
ENVIRONMENTAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Melvin E. Andersen, Bruno Hagenbuch, Udayan Apte, J. Christopher Corton, Tony Fletcher, Christopher Lau, William L. Roth, Bart Staels, Gloria L. Vega, Harvey J. Clewell, Matthew P. Longnecker
Summary: The study showed a positive correlation between serum cholesterol concentrations and exposure to PFOA and PFOS in humans, with only a small impact. Animal studies have not yet identified a mechanism that explains this association, and further research is needed to determine whether there is a causal relationship.
Article
Pharmacology & Pharmacy
Alina Efremenko, Pergentino Balbuena, Rebecca A. Clewell, Michael Black, Linda Pluta, Melvin E. Andersen, P. Robinan Gentry, Janice W. Yager, Harvey J. Clewell
Summary: Evidence shows that long-term exposure to arsenite results in significant changes in gene expression, including reversals in the direction of expression change in key regulatory genes. Cells treated with arsenic initially exhibit upregulation of oxidative stress responses and down-regulation of immune/inflammatory responses, followed by increased inflammatory and proliferative signaling, evidence of epithelial-to-mesenchymal transition, and alterations in DNA damage responses. The changing response of cells to arsenite over time appears to involve up-regulation of MDM2 by inflammatory signaling, leading to inhibition of P53 function.
Correction
Biochemistry & Molecular Biology
Lijuan Zhan, Hao Zhang, Qiang Zhang, Courtney G. Woods, Yanyan Chen, Peng Xue, Jian Dong, Erik J. Tokar, Yuanyuan Xu, Yongyong Hou, Jingqi Fu, Kathy Yarborough, Aiping Wang, Weidong Qu, Michael P. Waalkes, Melvin E. Andersen, Jingbo Pi
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Toxicology
Byron Kuo, Marc A. Beal, John W. Wills, Paul A. White, Francesco Marchetti, Andy Nong, Tara S. Barton-Maclaren, Keith Houck, Carole L. Yauk
Summary: Risk assessments are increasingly relying on in vitro assays for genotoxicity testing. This study evaluated 292 chemical datasets using the in vitro micronucleus test (MNvit) for hazard identification. The results identified 157 clastogenic chemicals, 25 negatives, and 110 inconclusive substances. In vitro to in vivo extrapolation (IVIVE) was used to convert concentrations into administered equivalent doses (AEDs), which were generally lower than points of departure (PODs) based on in vivo endpoints. Exposure estimates were utilized to calculate bioactivity exposure ratio (BER) values, identifying chemicals that may require additional testing.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Engineering, Environmental
Lei Dong, Zhiqiang Jiang, Lili Yang, Fen Hu, Weiwei Zheng, Peng Xue, Songhui Jiang, Melvin E. Andersen, Gengsheng He, M. James C. Crabbe, Weidong Qu
Summary: The study evaluated the health effects of nitrosamine mixtures in drinking water, revealing that mixed nitrosamines had greater genotoxic potential compared to individual compounds, while N-acetylcysteine could protect cells from chromosome damage.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Toxicology
Melvin E. Andersen
Summary: Octamethylcyclotetrasiloxane (D4) is a lipophilic compound that is highly volatile and has low water solubility. Animal studies have shown that D4 is toxic to several tissues when exposed to near saturating vapor concentrations or administered orally in vegetable oil vehicles. The toxicity of D4 is mediated through various mechanisms, including direct contact with epithelial cells in the lungs, interaction with nuclear receptor signaling pathways in the liver leading to hypertrophy and hepatocyte proliferation, and binding with alpha-2u globulin in the kidneys causing nephropathy.
TOXICOLOGY LETTERS
(2022)
Article
Pharmacology & Pharmacy
Peng Xue, Huihui Wang, Lili Yang, Zhiqiang Jiang, Hongliang Li, Qinxin Liu, Qiang Zhang, Melvin E. Andersen, M. James C. Crabbe, Lipeng Hao, Weidong Qu
Summary: Humans are exposed to disinfection by-products called HANs, which can lead to various health problems. In this study, it was found that NRF2-ARE activity plays a protective role against the cytotoxicity caused by HANs.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Amy J. Stefanowicz, Leslie Recio, Michael B. Black, Tyler Beames, Melvin E. Andersen, R. Allysa Stern, Rebecca A. Clewell, Patrick D. McMullen, Jessica K. Hartman, Aarati Ranade
Summary: Liver responses are commonly used as the basis for exposure standards, and the development of in vitro models is important to reduce reliance on animal models. This paper presents the development and evaluation of 2-D hepatocyte monoculture and 2-D liver cell co-culture systems using rat liver cells. The co-culture model showed more representative transcriptomic responses compared to intact rat models.
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2023)
Article
Toxicology
Jerry L. Campbell, Harvey J. Clewell III, Cynthia Van Landingham, P. Robinan Gentry, Athena M. Keene, Michael D. Taylor, Melvin E. Andersen
Summary: An updated PBPK model for manganese has been developed and successfully described the kinetics of manganese in tissues in both monkeys and humans. This model eliminates the need for relying solely on cadaver data and whole-body tracer studies to calibrate a human model, increasing the biological relevance and confidence in using the manganese PBPK models for risk assessment.
TOXICOLOGICAL SCIENCES
(2023)
Article
Toxicology
Rory B. Conolly, Jeffry Schroeter, Julia S. Kimbell, Harvey Clewell, Melvin E. Andersen, P. Robinan Gentry
Summary: Chronic inhalation of formaldehyde by F344 rats causes nasal squamous cell carcinoma (SCC), and the development of a biologically based dose-response (BBDR) model has provided dose-response conclusions for several international regulatory agencies. However, uncertainties prevented its use for cancer risk assessment by USEPA. This study presents an updated BBDR model that addresses uncertainties through refined dosimetry modeling and an extended dataset considering both exogenous and endogenous formaldehyde.
TOXICOLOGICAL SCIENCES
(2023)
Article
Toxicology
Malek Jomaa, Guillaume Pelletier, Denis Dieme, Jonathan Cote, Hamadi Fetoui, Andy Nong, Michele Bouchard
Summary: We conducted a study on rats to assess the effects of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). The study showed that dose and mixture exposure are important factors determining the toxicokinetics of REEs.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
J. L. Campbell Jr, H. J. Clewell III, C. Van Landingham, P. R. Gentry, M. E. Andersen
Summary: The PBPK model is used to correlate predicted tissue exposure to reactive metabolites with toxicity and carcinogenicity of CP.
FRONTIERS IN PHARMACOLOGY
(2023)