Estrogenic potency of chemicals detected in sewage treatment plant effluents as determined by in vivo assays with Japanese medaka (Oryzias latipes)

Abstract

Gonadal intersex and high prevalences of the female phenotype have been observed in fish populations in urbanized areas. Environmental estrogens discharged in sewage treatment plant effluents may be responsible for feminization of fish but many compounds with the potential to induce these responses occur in effluents, including natural and synthetic estrogen hormones, degradation products of alkylphenol ethoxylate surfactants, and plasticizers. In this study, the estrogen hormones 17 alpha-ethinylestradiol, 17 beta-estradiol, estrone, and estriol induced intersex (i.e., testis-ova) and altered sex in Japanese medaka (Oryzias latipes) when these fish were exposed to nanogram per liter concentrations of test compounds from hatch to approximately 100 d after hatch. A mix of nonylphenol mono- and diethoxylate induced a weak response and a mix of nonylphenol mono- and diethoxycarboxylate did not give a response in this assay at microgram per liter concentrations, indicating that these degradation products of nonylphenol ethoxylates have little or no estrogenic activity in fish. Bisphenol A induced testis-ova in medaka exposed to a concentration of 10 micrograms/L, but diethylhexyl phthalate did not induce a response. Results with the medaka assay were consistent with estrogenic responses in the yeast estrogen screening assay. Analyses of monitoring data reported in the literature indicate that concentrations of estrogen hormones detected in the final effluents of sewage treatment plants are generally greater than the lowest-observed-effect levels for alterations to gonadal development in medaka.

Assessment of Estrogenic Endocrine-Disrupting Chemical Actions in the Brain Using in Vivo Somatic Gene Transfer

“…In contrast to effects in fish (Metcalfe et al 2001; Staples et al 1998), the effects of BPA in amphibians are not well studied. Kloas et al (1999), using a static renewal exposure protocol, reported that BPA has estrogenic activity at 2.3 μg/L (~ 6.3 nM) and induces female-biased sex reversal in X. laevis .…”

“…For example, octylphenol, BPA, and EE2 all stimulate abnormal production of the egg yolk protein vitellogenin in male fish (Arukwe 2001; Sumpter and Jobling 1995). Moreover, BPA induced testisova in medaka exposed to a concentration of 10 μg/L (~ 27 nM) (Metcalfe et al 2001). Other studies showed that estrogenic EDCs cause sex reversal in frogs and feminization of secondary sex characteristics in fish (Arcand-Hoy and Benson 1998; Bogi et al 2002; Mackenzie et al 2003).…”

Long-Term Exposure to Environmental Concentrations of the Pharmaceutical Ethynylestradiol Causes Reproductive Failure in Fish

“…EE 2 concentrations are generally lower in surface waters than are natural steroidal estrogens, but the potency of EE 2 in fish is 10- to 50-fold higher than that of E 2 and E 1 in vivo (Segner et al 2003b; Thorpe et al 2003) due to its longer half-life and tendency to bioconcentrate (650- and 10,000-fold in whole-body tissues and bile, respectively) (Lange et al 2001; Larsson et al 1999). In fish, for example, only 0.1 ng/L EE 2 induces vitellogenin (VTG) yolk precursor (Purdom et al 1994), 0.1–15 ng/L can affect normal sexual development and differentiation (Andersen et al 2003; Metcalfe et al 2001; van Aerle et al 2002; Van den Belt et al 2003; Weber et al 2003), 2–10 ng/L can affect fecundity (Lange et al 2001; Scholz and Gutzeit 2000; Van den Belt et al 2002), 10 ng/L affects reproductive behavior (Balch et al 2004), and 1–10 ng/L can reduce the fertilization success or viability of embryos from exposed adults (Hill and Janz 2003; Lange et al 2001; Segner et al 2003a). Thus, given its concentration in the environment, EE 2 is potentially a major contributor to reproductive dysfunction in wild fish populations.…”

“…Little attention has been directed to the latter (Balch et al 2004). To fully assess the potential of EDCs to disrupt reproduction, multigenerational full life-cycle exposures are needed that consider all relevant life stages and developmental end points; even where fish have been exposed over their whole life-cycle, the impact of any resulting reproductive dysfunction on their reproductive output has mostly been overlooked in earlier studies (Metcalfe et al 2001; Van den Belt et al 2003). A major goal of this study was to determine which stages or reproductive components are relatively most sensitive to endocrine disruption in terms of population-level impairment or failure to allow better priority and focus for future studies.…”

Assessing the Sensitivity of Different Life Stages for Sexual Disruption in Roach ( Rutilus rutilus ) Exposed to Effluents from Wastewater Treatment Works

“…Steroid estrogens and some alkylphenolic chemicals are often found in WwTW effluents at concentrations sufficient to induce vitellogenic responses in laboratory exposures (Routledge et al 1998; Tyler and Routledge 1998). Natural steroid estrogens (Kang et al 2002; Koger et al 2000), the synthetic steroid estrogen ethinylestradiol (Metcalfe et al 2001), and alkylphenolic compounds (Gray and Metcalfe 1997; Gronen et al 1999) have also been shown to induce intersex in fish, but generally at concentrations higher than those present in WwTW effluent discharges. Steroidal estrogens and alkylphenolic chemicals (and other environmental estrogens) have also been shown to be interactive (additive) in their effects (Silva et al 2002; Thorpe et al 2001, 2003).…”