Toxicological report Bio 464 - PowerPoint Presentation

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Toxicological reportBio 464

E2

Background

E2 or 17

β

- estradiol is derived from female estrogen hormoneThe most potent form of mammalian estrogen steroidE2 and its synthetic derivative are important and relevant in ecotoxicology

BackgroundSynthetic form EE2 or

ethinyl

estradiol synthesized from estradiolEE2 is often used in oral contraceptives

Physical Properties

Fine

white

crystalline powder or creamEE2 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 CBoth 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 effectsEffects 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 chemicalsCarcinogenicStudy 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 spermStress response also shown to be affectedCortisol levels were depressed in male fish Effects not as pronounced in bivalvessusceptible to damage

by estrogens

at certain points in their

gametogenesis

process

Metabolism

Estradiol

is rapidly and completely absorbed from the gastrointestinal tractBioavailability 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

BibliographyD.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)

2977-2984

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