1. Toxicological report Bio 464

2. 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

3. Background
Synthetic form EE2 or ethinyl estradiol synthesized from estradiol
EE2 is often used in oral contraceptives

4. Physical Properties Fine white crystalline powder or cream
EE2 is a hemihydrate (one molecule of water for every two molecules of EE2)
EE2 E2

5. Physical property Solubility in water (low solubility)–
E2: deg C
EE2: deg C
Both are susceptible to photodegradation
EE2 more resistant to biodegradation

6. 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

7. 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.

8. 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

9. 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

10. 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

12. 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:
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: p. V (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

13. 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)
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