Products containing musk may cause early puberty. How should we choose cleaning products?

Produced by: Science Popularization China

Written by: Li Juan (PhD in Developmental Biology)

Producer: China Science Expo

Editor's note: In order to decode the latest mysteries of life science, the China Science Popularization Frontier Science Project has launched a series of articles called "New Knowledge of Life" to interpret life phenomena and reveal biological mysteries from a unique perspective. Let us delve into the world of life and explore infinite possibilities.

What are the effects of musk, which is commonly seen in palace fighting dramas?

In ancient costume dramas, it is not uncommon to use musk as a "weapon" in palace fighting. For example, musk is added to cosmetics or sachets to cause pregnant female characters to miscarry or even become infertile. These plots not only make people afraid of musk, but also arouse our attention to the relationship between musk and female endocrine and reproductive health.

Can musk really cause infertility or miscarriage?

Musk comes from the dried secretions of the glands between the navel and genitals of male musk deer. In ancient times, musk was used to treat female development and fertility-related diseases (such as dysmenorrhea, amenorrhea, etc.). However, musk also has the effects of stimulating the uterus and enhancing uterine contractions, which is why musk is often designed to cause miscarriage. The specific effects of musk have yet to be further verified by modern science.

musk deer

(Photo source: veer photo gallery)

In recent years, with the deepening of modern scientific research, scientists have found that musk has a complex composition, among which volatile substances such as musk ketone are its main chemical components, and these substances play a key role in pharmacological effects. However, what is worrying is that musk or its analogs are environmental endocrine disruptors (EDCs), which may have a significant impact on women's endocrine system.

EDC has hormone-like effects and is commonly found in bisphenol A in plastics, pesticide residues, and fragrances in daily chemical products [1]. They can imitate, block, or even interfere with hormones in the human body, causing the body system to "go haywire." The complex physiological process of puberty is naturally no exception. A recent study in August 2024 linked musk to early puberty or precocious puberty in women [2] .

The threat of puberty: the prevalence and harm of early puberty

People worry about early puberty or precocious puberty in children because early puberty may increase the risk of breast cancer, diabetes and heart disease in adulthood, may also cause shorter stature, and have a negative impact on children's mental health.

Adolescent Girls

(Photo source: veer photo gallery)

In today's society, the prevalence and trend of early puberty in girls have been confirmed by research. A large-scale study by Harvard University in 2024 surveyed more than 70,000 women born between 1950 and 2005 [3] and found that the average age of first menstruation for girls has been advanced and the average menstrual cycle has become longer. Among them, 15.5% of girls experienced early puberty (under 11 years old), and even 1.4% of girls started their first menstruation before the age of 9. The development of secondary sexual characteristics before the age of 8 for girls and before the age of 9 for boys can be considered precocious puberty.

You may ask, how does puberty occur?

This is a complex physiological process, which is mainly hidden in the fine regulation of hormones.

The "commander" of this process is the hypothalamus-pituitary-gonad axis, referred to as the HPG axis. The gonadotropin-releasing hormone (GnRH) released by the hypothalamus acts as a start signal, prompting the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones then act on the gonads to promote the secretion of sex hormones (such as androgens and estrogens), thereby triggering the appearance of secondary sexual characteristics and the maturation of the reproductive system.

obesity

(Photo source: veer photo gallery)

So, what factors can affect the normal work of the "Commander"? Scientists believe that genetic factors, overnutrition (obesity), certain diseases, and the environmental pollutants EDC mentioned above can disrupt the "Commander" to varying degrees and thus lead to early puberty.

Sunflower Musk: The "Youth Accelerator" Hidden in Daily Chemical Products

Musk Ambrette is a synthetic musk with a long-lasting and stable aroma that can be used in detergents and perfumes. In this latest study, the team of Dr. Menghang Xia and Natalie Shaw of the National Institutes of Health tested about 10,000 compounds in the laboratory using human cell lines and successfully found a number of "bad guys" that can activate key receptors in puberty, one of which is Musk Ambrette.

Experiments show that sunflower musk can open the "start lock" of puberty like a key, making the brain mistakenly believe that puberty is coming. In animal experiments, zebrafish exposed to sunflower musk looked no different from normal fish, but the brain area responsible for releasing puberty hormones was significantly enlarged. These experiments all suggest the potential impact of sunflower musk on human puberty development.

Uncovering the secret of sunflower seed and musk disrupting endocrine

What are the findings of the latest research by Dr. Menghang Xia and Natalie Shaw’s team?

First, the researchers used human HEK293 cells expressing sex hormone receptors to conduct a comprehensive screening of 10,000 environmental compounds included in the compound database. This is like looking for keys (candidate compounds) that can open a specific lock (sex hormone receptor) from a large warehouse. As a result, the researchers found some compounds that can "open" the locks of the two sex hormone receptors GnRHR and/or KISS1R, which can activate subsequent cellular responses.

Musk is one of them, which can specifically bind to KISS1R and trigger subsequent cellular responses. In addition, the researchers also identified five compounds that potentially interact with GnRHR for the first time, namely, formylcholine, bethanechol chloride, 2-(acryloyloxy)ethyltrimethylammonium, acetylcholine and carbachol.

To further confirm how the target compounds work, the researchers used a computer simulation technique called molecular docking to predict how the target compounds (keys) bind to the GnRHR and/or KISS1R receptors (keyholes).

They used the three-dimensional structure of the receptor (obtained from the Protein Data Bank) and the three-dimensional structure of the target compound (downloaded from the PubChem website) and had the computer try different binding modes and find the most stable binding mode.

This technology can show how compounds interact with receptors and how this interaction triggers specific physiological effects. The results suggest that ambrette can bind to the His309, Gln122, and Gln123 amino acid residues of KISS1R.

However, the above experiments are only conducted at the cellular level. So what discoveries will be made from experiments at the animal level?

Zebrafish

(Photo source: veer photo gallery)

The researchers used a commonly used model animal, the zebrafish. The GnRH neurons of this transgenic zebrafish emit green fluorescence, which makes it easier to directly observe the location and number of GnRH neurons. The researchers added sunflower musk to the culture medium in which the transgenic zebrafish embryos were grown, and they found that musk yellow could increase the number of zebrafish GnRH neurons and expand their distribution area in the brain.

In general, the most important message conveyed by this study is that EDCs such as ambergris may cause early puberty in women by activating GnRHR and/or KISS1R. The researchers will conduct population exposure studies to clarify the causal relationship between ambergris and early puberty in women, and the long-term effects of environmental compounds on reproductive system development and function are also important directions for future research.

Regulatory policies of various countries: protecting health and environment

In recent years, there have been many reports at home and abroad that synthetic musk has been detected in human blood, adipose tissue and breast milk, which is quite worrying. This has also led to more in-depth research on the bioaccumulation and potential toxicity of synthetic musk.

Musk is a type of nitromusk among artificial synthetic musks. Other synthetic musks include polycyclic musks, macrocyclic musks and alicyclic musks.

Synthetic musks are highly lipophilic and hydrophobic, difficult to degrade in the environment, and have a relatively persistent bioaccumulative effect. The main route of human exposure to synthetic musks is through skin absorption and accumulation in the body.

In order to protect public health, various countries have clear bans and regulations on synthetic musks.

According to Dr. Meng Xiangjing, editor-in-chief and chief researcher of the "Blue Book of China's Cosmetic Research Achievements (2022)", my country has listed umbel musk, ambrette musk and Tibetan musk as banned substances in the "Technical Specifications for Cosmetic Safety" (2015 edition), and clearly stipulated the types and limits of musks that can be used in perfumes; "GB/T 22731-2017 Daily Chemical Fragrances" has also included xylene musk in the banned list.

As early as 1993, Japan banned the use of some synthetic musks because they could disrupt the endocrine system. The EU has stricter regulation of synthetic musks. In 1995, it completely banned ambrette musk, in 1998 it banned the addition of umbel musk and Tibetan musk to cosmetics, in 2008 it listed xylene musk and ketone musk as "limited use", and banned them completely in 2013. The US IFRA (International Fragrance Association) has listed xylene musk as a banned ingredient.

List of banned ingredients for cosmetics

(Image source: "Technical Specifications for Safety of Cosmetics"

《Prohibited substances in daily fragrances》

(Image source: "Technical Specifications for Safety of Cosmetics"

In terms of supervision, my country officially implemented "GB/T 40844-2021 Determination of Artificial Musk in Cosmetics by Gas Chromatography-Mass Spectrometry" on May 1, 2022, which made detailed provisions for the identification methods of 11 kinds of artificial synthetic musks (including 5 banned and restricted nitro musks and 6 polycyclic musks) in cosmetics. This measure has further increased the public's confidence in the safety of daily chemical products.

Buy safely: Practical tips and warnings

What do parents need to pay attention to when choosing daily chemical products for children in their growth and development period?

The most important thing is to identify and avoid products containing potentially harmful synthetic fragrances. However, identification is difficult. For example, phthalates (PAEs), a common plasticizer and fragrance fixative, have been shown to be an endocrine disruptor that affects male hormone levels [4]. PAEs may be present in a variety of everyday products, including plastic toys, detergents, laundry products, etc. The product packaging may state it (such as phthalates), but it may also be hidden under the word "fragrance".

Dr. Meng Xiangjing gives suggestions on purchasing daily chemical products from the following aspects:

Learn to read the ingredient list : Before buying a product, carefully check the ingredient list. If the ingredient list contains known allergens or suspected harmful compounds, it is recommended to avoid purchasing it.

Choose regular brands : Buy products from regular channels and reputable brands. These products tend to have stricter quality control and strictly abide by the "Technical Specifications for Cosmetic Safety", "Regulations on the Supervision and Administration of Children's Cosmetics", and "Technical Guidelines for Children's Cosmetics".

Small area trial : Before using the product for the first time, you can try it on a small area of ​​skin. Observe whether there are allergic reactions such as redness, swelling, itching, etc. If there are no adverse reactions, continue to use it.

Beware of over-hype : Be wary of products that make exaggerated claims about their effectiveness. These products may contain compounds that have not been rigorously tested and may pose potential risks.

Conclusion

In recent years, scientists have gradually uncovered the mystery of how environmental compounds such as sunflower seed musk disrupt the endocrine system and cause early puberty in women. In the face of this potential hazard, the introduction of various regulatory policies has built a solid line of defense for us. Minors and teenagers should try to avoid using perfumes, and pay attention to the type of fragrance when purchasing detergents. Parents should also understand the hazards of harmful compounds such as synthetic musk, master the correct purchasing methods, and help children and adolescents avoid the influence of environmental endocrine disruptors, so as to protect every child's puberty.

References:

[1] Saqib Hassan, Aswin Thacharodi, Anshu Priya, R. Meenatchi, Thanushree A. Hegde, Thangamani R, HT Nguyen, Arivalagan Pugazhendhi, Endocrine disruptors: Unravelling the link between chemical exposure and Women's reproductive health, Environmental Research, Volume 241,2024,117385,

[2]Yang S, Zhang L, Khan K, Travers J, Huang R, Jovanovic VM, Veeramachaneni R, Sakamuru S, Tristan CA, Davis EE, Klumpp-Thomas C, Witt KL, Simeonov A, Shaw ND, Xia M. Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R. Endocrinology. 2024 Aug 27;165(10):bqae103. doi: 10.1210/endocr/bqae103. PMID: 39254333; PMCID: PMC11384912.

[3]Zifan Wang, Gowtham Asokan, Jukka-Pekka Onnela, Donna D. Baird, Anne Marie Z. Jukic, Allen J. Wilcox, Christine L. Curry, Tyler Fischer-Colbrie, Michelle A. Williams, Russ Hauser, Brent A. Coull, Shruthi Mahalingaiah. Menarche and time to cycle regularity among females born between 1950-2005 in the US. JAMA Network Open, May 29, 2024, doi: 10.1001/jamanetworkopen.2024.12854

[4] Yao Yuanyuan, Jia Xiuping, Li Zhenguo, et al. Research progress on phthalates in the environment. Frontiers of Environmental Protection, 2023, 13(6), 1281-1287