E2
Toxicological report
Bio 464
Background
 E2 or 17β- estradiol is derived from female estrogen
hormone
 The most potent form of mammalian estrogen steroid
 E2 and its synthetic derivative are important and
relevant in ecotoxicology
Background
 Synthetic form EE2 or ethinyl estradiol synthesized
from estradiol
 EE2 is often used in oral contraceptives
Physical Properties
 Fine white crystalline powder or cream
 EE2 is a hemihydrate (one molecule of water for every
two molecules of EE2)
EE2
E2
Physical property
 Solubility in water (low solubility)–
 E2: 3.60 mg/l @ 27 deg C
 EE2: 11.3 mg/l @ 27 deg C
 Both are susceptible to photodegradation
 EE2 more resistant to biodegradation
Source into the Aquatic Environment
 High level of E2 and EE2 often found in municipal,
agricultural and industrial wastewater outfall
 Human and excretion is a primary source of
xenoestrogens in an aquatic environment
 Increasing use of estrogen in medicine and farming
contribute to E2 and EE2 being found in aquatic
environment
Mechanism of Action
 At the cellular level, estrogens increase the synthesis
of DNA, RNA, and various proteins in target tissues.
Pituitary mass is also increased.
 As a lipophilic hormone, it diffuses readily through
cellular membranes to bind to estrogen receptors
situated in the nucleus.
Toxic effects
 Effects of an acute dose is mild and self-limiting
 LD50 > 5000 mg/kg in Rats via oral route
 Both E2 and EE2 are considered endocrine disrupting
chemicals
 Carcinogenic
 Study in rats show growth of tumors from chronic
exposure
 Chronic exposure in human increase risk of endometrial,
breast, and certain liver cancers
 E2 and EE2 have genotoxic effect on sperm cells
Toxic effects in aquatic systems
 Feminization shown in fish especially near wastewater
outfall sites
 Genotoxicity shown in male fish sperm
 Stress response also shown to be affected
 Cortisol levels were depressed in male fish
 Effects not as pronounced in bivalves
 susceptible to damage by estrogens at certain points in their
gametogenesis process
Metabolism
 Estradiol is rapidly and completely absorbed from the
gastrointestinal tract
 Bioavailability is reported at 40%
 Bioaccumulation is short term
 In rats and in humans, in that both species transform these
steroids mainly by (aromatic) 2-hydroxylation
 Estradiol is primarily converted to estriol, which is the
major urinary metabolite
 Ethinylestradiol is excreted in urine and feces in a ratio of
about 4:6
Bibliography
 V. Matozzo et al. Vitellogenin as a biomarker of exposure to estrogenic compounds
in aquatic invertebrates: A review. Environment International 34 (2008) 531–545
 W.J. Langston et al. Oestrogens and xeno-oestrogens in the aquatic environment.
Journal of the Marine Biological Association of the United Kingdom (2005)
 International Programme on Chemical Safety; Poisons Information Monograph:
Ethambutol (PIM 221) (1997) Available from, as of May 19, 2005:
http://www.inchem.org/pages/pims.html
 IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Man. Geneva: World Health Organization, International Agency for Research on
Cancer, 1972-PRESENT. (Multivolume work). Available at:
http://monographs.iarc.fr/index.php p. V72 503 (1999)
 E.L. Gregoraszczuk et al. Effects of estradiol, PCB3, and their hydroxylated
metabolites on proliferation, cell cycle, and apoptosis of human breast cancer cells.
Environmental Toxicology and Pharmacology 25 (2008) 227–233
 M. Teles et al. Biotransformation, stress and genotoxic effects of 17β-estradiol in
juvenile sea bass (Dicentrarchus labrax L.). Environment International 32 (2006)
470–477
Bibliography
 D.M. Papoulias et al. An in vivo model fish system to test chemical effects on
sexual differentiation and development: exposure to ethinyl estradiol. Aquatic
Toxicology 48 (2000) 37–50
 C.M. Ciocan et al. Effects of estrogen exposure in mussels, Mytilus edulis, at
different stages of gametogenesis. Environmental Pollution 158 (2010) 29772984
 M. Ann Rempel et al. Evaluation of relationships between reproductive metrics,
gender and vitellogenin expression in demersal flatfish collected near the
municipal wastewater outfall of Orange County, California, USA. Aquatic
Toxicology 77 (2006) 241–249