Abstract:
:Environmentally relevant mixtures of polycyclic aromatic hydrocarbons (PAHs; e.g., crude oils) are often rich in alkyl-PAHs, such as retene (7-isopropyl-1-methylphenanthrene), which produce dioxin-like toxicity in fish embryos. The mechanism of alkyl-PAH toxicity is not well understood but was previously thought to be mediated by cytochrome P4501A (CYPIA) enzymes. To understand the role of CYP1A in retene toxicity, we coexposed free-swimming rainbow trout (Oncorhynchus mykiss) embryos to 100 microg/L of retene and to a range of concentrations of 2-aminoanthracene (2AA; a known CYP1A inhibitor). Ethoxyresorufin-O-deethylase (EROD) assays of juvenile trout coexposed to 2AA and retene confirmed that 2AA inhibited CYP1A (median inhibitory concentration [IC50] for 2AA, 62 microg/L). In two independent trials, 2AA, both alone and in cotreatment with retene, produced a concentration-dependent increase in toxicity to embryonic trout. The toxicity resulting from 2AA alone is, to our knowledge, the first reported for embryonic stages of fish, with median lethal concentrations (LC50s) of 19 and 125 microg/L and overall sublethal median effective concentrations (EC50s) of 17 and 38 microg/L. Toxicity increased in embryos coexposed to retene and 2AA, resulting in LC50s of 14 and 17 microg/L of 2AA and overall EC50s of 7 and 3 microg/L of 2AA. The exposure-response curves for 2AA alone and for 2AA with retene were parallel, suggesting a common mode of action between the two treatment regimes and between retene and 2AA. Taken together with the juvenile EROD data, the toxicity of 2AA alone and in cotreatment with retene may be EROD (CYP1A) independent. The mixture toxicity was not consistent with previous coexposures to CYP1A inducers and inhibitors, suggesting that the current risk assessment model may not be a good predictor of PAH mixture toxicity.
journal_name
Environ Toxicol Chemjournal_title
Environmental toxicology and chemistryauthors
Scott JA,Ross M,Lemire BC,Hodson PVdoi
10.1897/08-461.1subject
Has Abstractpub_date
2009-06-01 00:00:00pages
1304-10issue
6eissn
0730-7268issn
1552-8618pii
08-461journal_volume
28pub_type
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