title: Route of exposure affects the oestrogenic response of fish to 4-tert-nonylphenol.
abstract: When toxicants cause effects to aquatic organisms, it is often unclear by what route, or routes, the toxicant entered the affected organism. The toxicity of a compound depends on its degree of uptake, distribution and metabolism, as well as its molecular interactions at the site of action. It was hypothesised, that a hydrophobic chemical such as 4-tert-nonylphenol (4-NP), entering via the gills/skin, may be more oestrogenic than one entering through the diet, because in the latter case it will undergo metabolism in the small intestine and liver before entering the bloodstream. In this way, metabolism may reduce or eliminate the oestrogenic potential of 4-NP before it reaches target organs such as the gonads or liver. To compare the potency of 4-tert-nonylphenol when administered via different routes, male fathead minnows (Pimephales promelas) were exposed to 4-NP either through waterborne exposure (experiment 1), or via the diet (experiment 2). Fish were exposed to 4-NP for 2 weeks either via the water at one of three nominal concentrations: 1, 10 or 50 microg/l (experiment 1) or 100, 500 or 1000 microg/day via the diet (experiment 2). Liver and blood samples were taken for vitellogenin mRNA and plasma vitellogenin quantification, respectively. Exposure of male fathead minnows to 50 microg/l of 4-NP in the water (experiment 1) and 500 and 1000 microg/day of 4-NP via the diet (experiment 2) induced vitellogenin mRNA. A similar pattern occurred for plasma vitellogenin induction, however, there was also a significant increase in plasma vitellogenin concentration in the fish exposed via the water to 10 microg/l of 4-NP. Using data from pharmacokinetics studies, an estimate for the total amount of 4-NP that entered the fish during each exposure was compared with the concentrations of plasma vitellogenin in each group of fish. The result showed a 10-fold greater sensitivity for 4-NP in fish exposed via the water compared with exposure via the oral route.Results obtained from this study indicate that a chemical such as 4-NP has a higher oestrogenic potential when it enters the bloodstream via the gills/skin of a fish compared with exposure through the diet.
mesh_terms: D000042:Absorption; D000818:Animals; D003530:Cyprinidae / Q000378:metabolism*; D004781:Environmental Exposure; D008297:Male; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D012333:RNA, Messenger / Q000097:blood; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D010636:Phenols; D012333:RNA, Messenger; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; C041594:4-nonylphenol