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Environmental Androgens and Antiandrogens: An Expanding Chemical Universe
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
L. Earl Gray, Vickie Wilson, Tammy Stoker, Christy Lambright, Johnathan Furr, Nigel Noriega, Phillip Hartig, Mary Cardon, Mitch Rosen, Gerald Ankley, Andrew Hotchkiss, Edward F. Orlando, Louis J. Guillette, William R. Kelce
Linuron is a urea-based herbicide with an acute oral LD50 in rats of 4000 mg/kg. Existing in vitro data demonstrate that linuron is a weak AR ligand15,27,71 with an EC50 between 64 and 100 µM. Lambright et al.15 reported that linuron competed in vitro with androgen for rat prostatic AR (EC50 = 100–300 µM) and human AR (hAR) in a COS cell whole cell binding assay (EC50 = 20 µM). Linuron also inhibited DHT-hAR induced gene expression in CV-1 and MDA-KB2 cells (EC50 = 10 µM).
Detection of anti-androgenic activity of chemicals in fish studies: a data review
Published in Critical Reviews in Toxicology, 2023
Grace H. Panter, Rebecca J. Brown, Alan Jones, Oliver Körner, Laurent Lagadic, Lennart Weltje
For the other fish tests (i.e. FSTRA, FSA, FSDT, M/ZEOGRT, MMT, FLCTT), no single test design or endpoint was consistent and reliable in detecting the anti-androgenic modality. Reported changes were also not consistent in endpoints across multiple studies where fish were exposed to the same anti-androgen at similar concentrations (i.e. results from the validation of the FSTRA and MMT; OECD 2006 and US EPA 2013, respectively). The inconsistency in the observed anti-androgenic effects might be explained by experimental issues, lack of potency, systemic toxicity, feedback mechanisms, sensitivity of the species tested, or mechanism of action confounded by other endocrine activities. For example, although spironolactone was identified as a model anti-androgen in the AR Bioactivity Model, it caused masculinising effects (increase/induction of SSC) in exposed male and female fish (LaLone et al. 2013). In vitro studies with mammalian cell lines have indicated that spironolactone possesses significant androgenic activity (as discussed in LaLone et al. 2015), so its anti-androgenic activity could be confounded by another endocrine activity. Linuron, a substance shown to be inactive in this review, is thought to act via mixed mechanisms as an AR antagonist and inhibitor of foetal testosterone (Wilson et al. 2008).
Exposure to pesticides and oxidative stress in Brazilian agricultural communities
Published in Biomarkers, 2021
Aline de Souza Espindola Santos, Christine Gibson Parks, Mariana Macedo Senna, Leandro Vargas B. de Carvalho, Armando Meyer
In this rural Brazilian population, oxidative stress biomarkers were not associated with overall pesticide use. However, our results suggest some possible associations between regular use of pesticides and oxidative stress. In particular, a positive association was seen between levels of 8-ISO and the commonly used herbicide glyphosate. Use of two fungicides, difenoconazole and copper sulphate, and the insecticide methomyl were positively associated with GPx activity, an enzyme that specifically scavenges organic peroxides. Living in or close to agricultural fields was also positively associated with GPx activity. Use of the fungicide copper sulphate and the herbicide linuron was positively associated with GST activity, an enzyme that neutralises reactive metabolites during xenobiotic metabolism, while the insecticide deltamethrin was negatively associated with the activity of this enzyme.