EU Scientific Committee’s final opinion on potential endocrine disrupters genistein and daidzein use in cosmetics

05 Oct 2022 --- The Scientific Committee on Consumer Safety (SCCS) is sharing its final opinion on the use of the aglycone form of genistein and daidzein in cosmetics while factoring in its potential endocrine-disrupting (ED) properties. The compounds are currently used in cosmetics as antioxidants, skin protectants and skin and hair conditioning agents.

Based on the safety assessment of available data on genistein and daidzein, the SCCS concludes that genistein can be safely used in cosmetic products up to a maximum concentration of 0.007%.

Daidzein can be safely used in cosmetic products up to a maximum concentration of 0.02%.

“Currently, genistein and daidzein are not regulated under the Cosmetic Regulation (EC) No. 1223/2009,” shares the Opinion.

Reproductive role
The two compounds are phytoestrogens (plant estrogens) found in legumes in glucoside forms. Phytoestrogens affect the body as estrogen does.

In the SCCS opinion, phytoestrogens are defined as plant-derived compounds with structural similarity to 17β-estradiol, a steroid hormone produced primarily by the ovaries during the reproductive lifespan.

It also plays a role in developing female secondary sexual characteristics and the maintenance of the female reproductive tract.Genistein can be safely used in cosmetic products up to a maximum concentration of 0.007%.

“Among the phenolic compounds classified as phytoestrogens are isoflavones, which are typically found in legumes, including soybeans, chickpeas, fava beans and fruits and nuts (pistachios, peanuts, etc.),” continues the Opinion.

“Orally ingested isoflavones are enzymatically metabolized in the gut and the liver, and by microorganisms in the intestine.”

Cosmetic uses of isoflavones
Among common isoflavones are genistein and daidzein, which are “used in the formulation of leave-on cosmetic products.”

The SCCS reports that the cosmetic activities of isoflavone extracts are mainly for collagen synthesis stimulation, as an enhancer of hyaluronic acid production, free radical formation limitation, anti-inflammatory activity and antioxidant activity.

“Therefore, cosmetic products with isoflavones extracts, including genistein and daidzein, are mainly used in anti-aging products,” concludes the SCCS.

Overall comments on toxicokinetics and reprotoxicity
Based on an extensive scientific literature roundup and tests, the SCCS finds:

“The concentration of unconjugated genistein in plasma in humans is very low. This is an important consideration for safety assessment because the conjugated form has relatively little biological activity.”

“The evidence from a multigenerational study in rats indicates that genistein produces developmental toxicity in terms of a transient decrease in the F1 and F3 pup body weights following dietary exposure to 5, 100, and 500 ppm via oral administration,” continues the SCCS.

Daidzein is well absorbed in humans, but it is not possible to derive a reliable percentage from current data as the information indicates that human isoflavone bioavailability depends on the relative ability of gut microflora to degrade these compounds.

“For daidzein, the available information on human toxicokinetics is limited. Most studies refer to the isoflavone or glycosidic form of daidzein, which is of limited relevance for the safety evaluation of daidzein in aglycone form used in cosmetic applications,” continues the SCCS.

“As daidzein has also been associated with an estrogenic mode of action, the endocrine potential that may lead to adverse effects needs to be investigated before conclusions can be drawn about the reprotoxicity of this compound.” Daidzein can be safely used in cosmetic products up to a maximum concentration of 0.02%.

Overall comments on genotoxicity/mutagenicity
Based on an extensive review of existing scientific literature, the SCCS concludes that genistein shows no evidence for mutagenicity in the bacterial gene mutation test. However, in vitro mammalian gene mutation studies show positive results indicating the mutagenic potential of genistein.

While considering in vivo mammalian gene mutation studies on Big Blue transgenic rats, the SCCS

considers that genistein does not pose a gene mutation hazard in vivo.

“Although the available results of the in vitro bacterial gene mutation studies…as well as of the in vitro mammalian cell gene mutation studies…do not allow drawing firm conclusions, the SCCS, after analysis of the high relevance in vivo mammalian cell gene mutation studies with negative results,” shares the SCCS.

“Considering all the available data on daidzein genotoxicity, the SCCS is of the opinion that daidzein does not pose a genotoxicity hazard in vivo.”

Overall comments on carcinogenicity and ED potential
Considering the available evidence from published studies, the SCCS concludes: “Genistein is nongenotoxic in vivo and does not exhibit a carcinogenic potential.”

“Daidzein Carcinogenicity data are not available for daidzein. However, there is a huge amount of literature investigating possible associations between the intake of soy isoflavones and various cancer types.”

On the ED potential of genistein and daidzein, both “have a weak binding affinity to estrogen receptor in vitro. Significant endocrine-related effects in vivo were observed in rodents and were only reported at high doses.” Daidzein and Genistein are often used in anti-aging products.

“With the collective view of the available information, the SCCS considers that the toxicological point of departure (PoD) selected for the safety assessment of genistein also adequately covers its endocrine-related effects.

When the review started
In 2019, the EC carried out a public call for data on 14 of the 28 ED substances to prepare for their safety assessment – in which genistein and daidzein were included. The 28 substance list was consolidated in 2019 based on stakeholder consultation.

This resulted from an EC review of the Cosmetic Regulation 1223/2009 in 2018 regarding substances with ED properties.

The SCCS provides the EC with scientific advice when preparing policies and proposals relating to consumer safety, public health and the environment. The opinions do not necessarily reflect the views of the commission.

By Venya Patel

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