Genistein and estrogen

Hazard identification Food Toxicology

1- Information on the compound

Chemical property

Value (+ unit)

Reference

Molecular structure

C15-H10-O5

ChemId plus website

Molecular weight

270.24

National Toxicology Program website, 2010

CAS number

446-72-0

Chemindex website, 2010

Log Kow

2.84 (est.)

National Toxicology Program website, 2010

Solubility

Soluble in the usual organic solvents; soluble in dilute alkalies with yellow color. Practically insoluble in water.

National Toxicology Program website, 2010

Henry constant

5.1 x 10-17 atm-cu m/mole at 25 deg C (est)

National Toxicology Program website, 2010

Half-life (per medium, if relevant per condition)

What is (are) the main route(s) of (bio)degradation

Bacterial degradation of genistein (hydrolysis) followed by conjugation to glucuronic acid and sulfate, catalysed by phase II enzymes, leads to an excretion through bile and urine in human.

Yeh, 2003

Steensma, 2006

Special feature or use of the compound

Genistein is an isoflavone belonging to the group of phytoestrogens.

NTP-CEHR, 2006

Genistein is an isoflavone that shares similarities in structure to estrogen and is able to interact with estrogen receptors (Mazur, 2000). Glycosides such as genistin, formed by the conjugation of genistein to a sugar molecule, are the predominant form of genistein in unfermented soy products (NTP, 2006; COT report, 2003). Genistein present unconjugated as aglycones comprises only a small amount in unfermented soy products, whereas in fermented food products, aglycones are predominant (NTP, 2006; COT report, 2003). Genistein is a hydrophobic compound, and as a consequence nearly insoluble in water (National Toxicology Program website, 2010; COT report, 2003). Nevertheless, the water solubility may increase after conjugation to glucose, glucuronide or sulfate groups (COT report, 2003). After genistein is consumed, glycosides can be deconjugated by bacterial enzymes, β-glucuronidase or arylsulfatase, in the gut (Yeh, 2003 and references therein). After hydrolysis is completed, metabolites can be absorbed or further metabolized by microflora that are predominantly present in the colon (Yeh, 2003 and references therein). When aglycones reach the small intestine, they are quickly absorbed since these compounds have a lower polarity and molecular weight compared to the glycosides (Yeh, 2003 and references therein). In the colon, de-conjugated genistein and unabsorbed aglycones are degraded to dihydrogenistein followed by the formation of 6'-hydroxy-demethylengolensin (Yeh, 2003; Steensma, 2006). Further degradation may eventually lead to the metabolic product 4-ethyl phenol (Steensma, 2006). In the liver genistein is conjugated for the greater part to glucuronic acid by UDPGT, conjugation to sulfate by sulfotransferase enzymes takes place to a smaller extend (Steensma, 2006; NTP, 2006). The formed metabolites may undergo enterohepatic circulation and biliary excretion may follow (Yeh, 2006; NTP, 2006). In the urine, genistein is excreted as a monoglucuronide, diglucuronide, and as a sulfoglucuronide (Steensma, 2006; Alderkreutz 1995). An overview of several chemical properties of genistein can be found in table 1.

Referenties bekijken!

2-Basic info Framework of the risk assessment

Background info

Facts

Reference

Used for

Genistein can be extracted from soy and other beans. It is used as an anti-neoplastic and anti-tumor agent. à rewrite??

NTP-CERHR, 2006

ChemID plus website

Sources (where/how is it produced and reaches food/drinking water)

Soybeans are the most important source of genistein. In addition, other legumes such as lentils and chickpeas comprise relatively low quantities of genistein.

NTP, 2007

NTP-CERHR, 2006

COT report, 2003

Especially present in

Human exposure to genistein mainly occurs through the consumption of foods that consist of soybeans and/or soy protein, including dietary supplements and soy-based infant formula.

NTP, 2007

NTP-CERHR, 2006

Specifically exposed people

Eastern populations, vegans and vegetarians may be specifically exposed to genistein as a result of higher dietary intakes.

NTP, 2006

McCauley, 2005

COT report, 2003 and references therein

Genistein is a naturally occurring compound that can be found in some legumes, principally soybeans (NTP, 2007; NTP-CERHR, 2006; COT report, 2003). Consequently, genistein can be found in a wide variety of soy based foodstuffs. Some examples are tempeh, soy milk and tofu (NTP-CERHR, 2006 and references therein). Depending on the method of processing, many soy foods contain a relatively amount of genistein (COT report, 2003). However, not only the method of processing influences the quantity of genistein in soy products, differences in geographic location were the soy is grown, climate, and harvesting procedures, may cause variations in the level of genistein (COT report, 2003). Since the Asian diet consist for a significant part of soy products, consumers of such a diet may reveal high plasma levels of this isoflavonoid. Traditional Asian diet contains high levels of soy. Therefore, Asiatic people are specifically exposed to genistein. NTP, 2006; McCauley, 2005; COT report, 2003 and references therein) à stukje herschrijven!!!!

Steensma: The content of isoflavones varies with the crop variety, geographic location, soil type, crop year and environmental factors

NTP, 2006: Setchell et al. (5) stated that isoflavone levels in soybeans can vary as a result of geographic location, climate, and growing conditions.

COT 2003: Phytoestrogens are natural constituents of many plants, seeds and grains. There is considerable variation of phytoestrogen concentrations in different plants. A number of factors can influence the phytoestrogen content including, species and strain differences and environmental conditions. Processing can also alter the phytoestrogen content of foodstuffs.
Vegan or vegetarian diets may have higher intakes of phytoestrogens compared with the general population, due to the consumption of soy-based meat and dairy replacement foods.

3- Hazard identification

Give qualitative info on the possible toxic effects without worrying about specific doses/concentrations.

Toxic effects

Facts + species

Reference

General toxicity (what is found at high acute or at low chronic exposure)

Human

Animal (lab)

Other animals

Specific toxicity (name mechanism of specific effects)


Specific effects (are specific groups of people extra vulnerable for this compound?)


Describe the potential toxic effects (qualitative) of the compound in your own words, based on the info you collected above. Often there are wanted and unwanted toxic effects, eg. in the case of pesticides.

References

Chemindex http://search.ccinfoweb.ccohs.ca/ccohs/jsp/search/search.jsp?QueryText=genistein&MaxDocs=500&ResultStart=1&SortSpec=Score+desc&hTab=7&vTab=1&hideTabs=F&Coll=cid

Chemid plus http://chem.sis.nlm.nih.gov/chemidplus/ProxyServlet?objectHandle=DBMaint&actionHandle=default&nextPage=jsp/chemidheavy/ResultScreen.jsp&ROW_NUM=0&TXTSUPERLISTID=000446720

National Toxicology Program website http://ntp.niehs.nih.gov/index.cfm?objectid=E87FE570-BDB5-82F8-F75D9BD07B3131C5

NTP National Toxicology ProgramToxicity Report Series Number 79

NTP Technical Report on the Reproductive Dose Range-Finding Toxicity Study of Genistein (CAS No. 446-72-0) Administered in Feed to Sprague-Dawley Rats October 2007 National Institutes of Health Public Health Service U.S. Department of Health and Human Services

Breast cancer, Asian diet, and soy genistein - a matter of all or nothing? Author(s): Lindsay McCauley, Barbara Demmig-Adams Journal: Nutrition & Food Science Year: 2005Volume:35Issue:1Page:28-34 Publisher: Emerald Group Publishing Limited 1993 Nov 13;342(8881):1209-10. Plasma concentrations of phyto-oestrogens in Japanese men.

Mazur, W. and Adlercreutz, H. (2000) Overview of naturally occurring endocrineactive substances in the human diet in relation to human health. Nutrition 16, 654-658.

Adlercreutz, H., Van der Wildt, J., Kinzel, J., Atalla, H., Wähälä, K., Mäkelä, T., Hase, T. and Fotsis, T. (1995) Lignan and isoflavonoid conjugates in human urine. Journal of Steroid Biochemistry Molecular Biology 52, 97-103.

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