Possible androgenic/anti‐androgenic activity of the insecticide fenitrothion

Abstract

To date, within the field of endocrine disruption, much focus has been placed on chemicals that mimic oestrogens (so-called xenoestrogens), and the number of such chemicals apparently detected continues to grow steadily. Less effort has been expended on investigating chemicals that mimic, or antagonize, other hormones. Nevertheless, a number of chemicals have been reported to have a weak affinity for the androgen receptor, all of which have, to date, been found to have anti-androgenic activity in vivo. In this report, we present evidence that the insecticide fenitrothion can interact with the androgen, but not with the oestrogen, receptor. Using recombinant yeast expressing the human androgen receptor, we found that fenitrothion behaved as an androgen agonist in vitro when tested alone, and that it could antagonize the androgen DHT when both chemicals competed for the androgen receptor in vitro. In vivo studies using both intact and castrated male rats showed no conclusive androgenic or anti-androgenic responses. Changes in organ weights suggestive of anti-androgenic effects were mitigated against by the reduced body weights of fenitrothion-treated rats. The toxicity of the compound precluded the use of higher dose levels to substantiate any tentative findings. Interestingly, fenitrothion (and related insecticides) is structurally similar to flutamide, an anti-androgen used clinically that gives clearly positive responses in both intact and castrated rats.

Estrogenic and Anti-androgenic Activity of Nitrophenols in Diesel Exhaust Particles (DEP)

“…28,29) Furthermore, Sohoni et al have determined by hAR-yeast assay that parathion and fenitrothion possess androgenic and anti-androgenic activity and fenitrothion inhibits the stimulatory effect of testosterone propionate on Cowper's gland in the rat. 30) It was found that nitrophenols isolated from DEP possessed not only vasodilatory activity but also estrogenic and anti-androgenic activity. Furthermore, our results suggest that, as a result of diesel exhaust emission or the degradation of various pesticides, the accumulation of nitrophenols (including PNP and PNMC) in the air and soil could have serious deleterious effects on wildlife and human health though disturbance of endocrine and cardiovascular functions.…”

Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

“…Antiandrogenic compounds so far reported include vinclozolin, linuron, iprodione, chlozolinate, procymidone, flutamide, p,p´-DDE, and ketoconazole (Gray et al 1999a(Gray et al , 1999bLambright et al 2000;McIntyre et al 2000;Ostby et al 1999;You et al 1999). In contrast, both positive and negative results on the antiandrogenic activity of fenitrothion, a relative of fenthion, have been reported (Ashby and Lefevre 2000;Curtis 2001;Sohoni et al 2001;Sunami et al 2000;Tamura et al 2001). The significant antiandrogenic activity of fenitrothion found in our study supports previous findings that fenitrothion has antiandrogenic properties.…”

Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats

“…These situations provide the p o t e n t i a l f o r e n v i r o n m e n t a l e x p o s u r e t o permethrin and its attendant human health risks. Many pesticides have been reported to possess estrogenic or androgenic activities [15][16][17][18][19][20][21][22], and thus are classified as endocrine disruptors. However, relatively few studies have reported on the estrogenic and androgenic activities of permethrin [3,[23][24][25][26], and the results of the studies are in some respects contradictory.…”