Antiandrogens toxicity

Kelce, W.R., Monosson, E., and Gamcsik, M.P. et al. (1994). Environmental hormone disrupters—evidence that Vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicology and Applied Pharmacology 126, 276-285. 

Spironolactone Block cytoplasmic aldosterone receptors in collecting tubules of nephron possible membrane effect Increased salt and water excretion reduces remodeling reduces mortality Chronic heart failure aldosteronism (cirrhosis, adrenal tumor) hypertension Oral duration 24-72 h (slow onset and offset) Toxicity Hyperkalemia, antiandrogen actions... 

Gray LE, Wolf C, Lambright C, et al. 1999. Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinatc,/ ./ -DDE, and ketoconazole) and toxic substances (dibutyl-and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformation in the male rat. Toxicol Ind Health 15 94-118. 

W.R. Kelce, E. Monosson, P. Gamcsik, S.C. Laws and L.E. Gray Jr., Environmental hormone disruptors Evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol. Appl. Pharmacol. 126 276, 1994. 

Recent work with models both in vivo and in vitro shows that fenthion also has antiandrogenic activity and can produce oxidative stress. More research is needed to establish whether these mechanisms are responsible for significant toxic effects. 

D. Toxicity Cimetidine is a potent inhibitor of hepatic drug-metabolizing enzymes and may also reduce hepatic blood flow. Cimetidine also has significant antiandrogen effects in patients receiving high doses. Ranitidine has a weaker inhibitory effect on hepatic drug metabolism neither it nor the other H, blockers appear to have endocrine effects. 

Methoxychlor is a reproductive toxicant. Exposure of young adult male rats to methoxychlor reduced their serum testosterone levels (Murono et al. 2006). It metabolized in the liver into 2,2-bis(p-hydroxyphenyl)-l,l,l-trichloroethane and both methoxychlor and its metabolite were found to exhibit weak estrogenic and antiandrogenic activities. Flynn etal. (2005) have reported that long-term exposure to methoxychlor in diet altered the sexually dimorphic behavior in young rats of both sexes. The study indicated that consumption of sodium solution increased in rats from such exposure. The toxicity of methoxychlor, particularly in the central nervous system, may be attributed to its inhibition of brain mitochondrial respiration which probably is caused by an increased production of reactive oxygen species (Schuh et al. 2005). 

Fig. 7 Noimalized activity distributions (%) across 6 particle size fractions grey and black, from left to right 7.2-10.0, 3.0-7.2, 1.5-3.0, 0.95-1.5, 0.45-0.95 and <0.45 pm of aerodynamic size) and of the gaseous phase (white) of antiandrogenicity (AA, in the presence of testosterone), antiestrogenicity (AE), dioxin-like activity (AhR), and genotoxicity (Gen), and PAH (sum of 28 substances) calculated dioxin-like toxicity (TEQ) together with particulate matter mass (m) and specific surface (S) size distributions sites in the Brno area, a city (urban), b airport (urban), c Kyjov (urban), and d Ivan (rural). Effects too low to derive IC25 values are reflected as zero...

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