Extended exposure (14 weeks) to the lowest dose

(0.02 mg AP kg−1) gave similar results (Meier et al., 2011). These exposure levels are difficult to compare with real-life exposure to PW plumes, especially since many endocrine disruptors seem not to produce linear dose–response curves (Vandenberg et al., 2012), but the authors themselves consider the exposure level higher than what is realistic, possibly demonstrating a worst-case disturbance of reproductive fitness in the cod. Also, Sundt and Bjorkblom (2011) recorded impaired oocyte development and reduced estrogen levels in pre-spawning female Atlantic cod, as well as altered testicular development, an increase in the amount of spermatogonia and primary spermatocytes, and a reduction in the amount of mature sperm in males following exposure to realistic concentrations of PW (0.066–0.2%) for twelve weeks. Therefore, one cannot exclude that APs in PW effluents under certain circumstances could cause reproductive buy FDA approved Drug Library disturbance in sensitive stages (e.g. pre-spawning) of wild fish that stay close to offshore platforms for long periods of time. However, it seems unlikely that this could see more affect a significant fraction

of Atlantic cod populations. Estrogens are involved in many biological processes, including control of gonad maturation in male and female fish. The enzyme cytochrome P450 aromatase converts androgens, like testosterone or androstenedione to estrogen (E2) and estrone. Montelukast Sodium Teleost fish have two aromatase genes; one that is mainly expressed in the gonads (aromatase A or cyp19a1a), and one that is mainly expressed in the brain (aromatase B or cyp19a1b) ( Diotel et al., 2010). Meier et al. (2011) did not find any regulation of cyp19a1a in the ovary

(mRNA expression or enzyme activity), or of aromatase activity in the brain of female cod exposed to AP or PW. The specific activity of aromatase in the ovary was therefore not affected by the AP-exposure. Tollefsen et al. (2007) and Thomas et al. (2009) used recombinant yeast estrogen and androgen screens to determine the in vitro estrogen receptor (ER) agonist and androgen receptor (AR) antagonist potencies of solid phase extracts (SPE) of PW collected from 20 Norwegian installations. They found estrogenic activities at levels equivalent to <0.1–4 ng L−1 E2 (dependent on PW source), similar to those previously reported for the UK continental shelf (UKCS) ( Thomas et al., 2004). No activity was detected after exposure to filtered oil droplets from PW suggesting that ER activity was primarily associated with the dissolved phase. Thomas et al. (2009) identified short-chain petrogenic APs to be responsible for around 35% of estrogen receptor (ER) agonist activity measured in vitro. Androgen receptor (AR) antagonists were detected both in the dissolved and oil associated phase. They also reported that naphthenic acids, which occur in significantly higher concentrations than C4–C7 APs in PW, were weak ER agonists.