What are endocrine disruptors?

The next several posts will be devoted to the subject of endocrine disruption with a focus on environmental chemicals that interfere with sex steroids, chiefly estrogens and androgens. Most people are probably familiar with estrogen and testosterone. These are steroids produced by the human body (and the bodies of other species) that play important roles in sexual development and reproduction. They also play many other related roles, influence growth and tissue maintenance, neurological function and behavior.

 An endocrine disruptor is a chemical agent that interferes with very complex, inter-regulating and intertwined endocrine systems. Interference with one steroid hormone can produce chain reactions that impact other hormones that, in turn, influence other systems and other hormones. For example, Bisphenol A, an estrogen mimic will change production of Prolactin (Steinmetz et al. 1997).

A young boy ponders something.

The effects of endocrine disruptors can be strongest during critical periods such as fetal development, infancy, adolescence, conception and pregnancy. These are times of important changes that will have long-term consequences for a child (fry, larvae, pup, chick etc.) and its future children. Thousands of chemicals have been found to be endocrine disruptors. Some of them are very resistant to degradation and remain in the environment and in people's bodies for decades or longer. Many of these are no longer in use even though with can still easily detect them. They were found to be a threat to health and were banned and/or replaced with something less dangerous. There are many other chemicals in use that have not been tested. There are others that are current foci of research and debate. These chemicals were not developed to cause harm to humans (at least not most of them), rather they were found to be harmful after they were already in use. An example that you may be aware of is the plastics additive Bisphenol A.

Bisphenol A is commonly called BPA. After years of debate and conflict among interested parties BPA has been banned from baby bottles in the US. Manufacturers are adapting and produced new products. Consumers can easily find BPA-Free materials and it seems likely that BPA will leave many markets.  While BPA may be in decline the issue of endocrine disruptors is far from resolved. The plastic products used to make some BPA-Free plastics also appear to be endocrine disruptors (Yang et al. 2011.) Some of them appear to be more disruptive than the BPA-laced plastics they are meant to replace.  It would be better to produce Endocrine-Disruptor-free products Instead of  BPA-Free products

It is very difficult to pull something out of the market once it is already there. People's livelihoods have become dependent on continuing use, reputations are at stake, there may be millions of dollars spent on legal fees,  on efforts to fund studies that would show that the product in question was harmless after all, and then more time and more money spent arguing why banning a product would be unfeasible and not worth the cost of replacing it, developing alternative technology, or cleaning up environmental messes. Banning chemicals after they become part of the economy is hugely wasteful, makes people on both sides of the playing field upset and erodes public confidence. We may discuss this in greater detail later, but for now, just be aware that the chemical problem of endocrine disruptors is also an economic and then a political problem as well. This should be resolved eventually, but until then, we may have a very interesting, and for some a painful, ride. Steinmetz R, Brown NG, Allen DL, Bigsby RM, & Ben-Jonathan N (1997). The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. Endocrinology, 138 (5), 1780-6 PMID: 9112368 Yang CZ, Yaniger SI, Jordan VC, Klein DJ, & Bittner GD (2011). Most plastic products release estrogenic chemicals: a potential health problem that can be solved. Environmental health perspectives, 119 (7), 989-96 PMID: 21367689

Steinmetz R, Brown NG, Allen DL, Bigsby RM, & Ben-Jonathan N (1997). The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. Endocrinology, 138 (5), 1780-6 PMID: 9112368  

Yang CZ, Yaniger SI, Jordan VC, Klein DJ, & Bittner GD (2011). Most plastic products release estrogenic chemicals: a potential health problem that can be solved. Environmental Health Perspectives, 119 (7), 989-96 PMID: 21367689

Are Silver Nanoparticles in Clothing Safe?

Silver nanoparticles are woven into high-tech athletic clothing as a means of controlling bacteria and odors.  Silver has low toxicity for people, but is able to kill bacteria.  How it kills bacteria is not completely understood, but it is believed to cause oxidative stress.  Oxidative stress is harmful for us as well, but bacteria can be killed at lower levels than can hurt us.  Still, oxidative stress is not good.  That's why anti-oxidants are protective against cancer and effects of cell damage.  Silver nanoparticles are used in topical antibiotics to treat life threatening infections in burn patients.  Better to risk a little oxidative stress from silver nanoparticles than to die from an infection. 

So, is it a good idea to put silver nanoparticles in clothes? No one knows the answer to this question.  But there are a few answers to a few related questions.  For example, do the silver nanoparticles embedded in fabrics some off the cloth and end up in wastewater?  Do the particles come off the cloth and enter peoples bodies? Are there any known health effects from exposure to silver nanoparticles?  If the particles stay in the fabric there is probably little to worry about.  Let's take a look:

• Do Silver nanoparticles come off the fabrics in which they are embedded?  Apparently they do, but different fabrics lose nanoparticles at different rates, at least during the wash cycle. Benn TM, & Westerhoff P (2008). Nanoparticle silver released into water from commercially available sock fabrics. Environmental science & technology, 42 (11), 4133-9 PMID: 18589977
•  Can silver nanoparticles be absorbed through people's skin?  Apparently they can.  Silver nanoparticles are being used a a topic anti-biotic in burn patients.  Infection is a major, major factor in recovery (and mortality) for burn patients.  Brandt O, Mildner M, Egger AE, Groessl M, Rix U, Posch M, Keppler BK, Strupp C, Mueller B, & Stingl G (2012). Nanoscalic silver possesses broad-spectrum antimicrobial activities and exhibits fewer toxicological side effects than silver sulfadiazine. Nanomedicine : nanotechnology, biology, and medicine, 8 (4), 478-88 PMID: 21839058
  
• How long do silver nanoparticles stay in a person once they get there?  This is an important question.  If they stay around a long time, they can do damage for a long time.  If they leave quickly they would be less dangerous.  Same thing goes for a lot of other substances.  The answer to this question appears to be unknown 
• Are there any known health effects if silver nanoparticles are absorbed?  Lim DH, Jang J, Kim S, Kang T, Lee K, & Choi IH (2012). The effects of sub-lethal concentrations of silver nanoparticles on inflammatory and stress genes in human macrophages using cDNA microarray analysis. Biomaterials, 33 (18), 4690-9 PMID: 22459196.  Silver nanoparticles appear to have harmful effects on some human (and animal) cells.  (Comparative in vitro cytotoxicity study of silver nanoparticle on two mammalian cell lines- citation)

While its been demonstrated that the particles can harm cells, tissues or organs we don't know how much would be needed to harm health.  The amount of silver nano-particles absorbed from clothing may not be high enough to matter.  Its an unanswered question.   We'll probably hear more about this in coming years.  For now you'll have to rely on your own judgement.

High Fat Diet, Cholesterol, the Swiss and the Australian Aboringinals

Perusing Google News with morning I came across an article claiming that "Research Shows CrossFit Diet/Exercise Reduces Risk of Heart Disease". I clicked on that one immediately because, to the best of my knowledge, no scientific research has been published on relationships between high intensity CrossFit-type training and cardiovascular disease. If one were to do a search today on Web of Knowledge using the search term "Crossfit" you would get a single hit:

Jansen, J., van Dam, N., Hoefsloot, H., & Smilde, A. (2009). Crossfit analysis: a novel method to characterize the dynamics of induced plant responses BMC Bioinformatics, 10 (1) DOI: 10.1186/1471-2105-10-425

I'm sure the intentions of whoever wrote the press release were good . . . but . . . it is quite a stretch. Still, interesting that it made it into Google News. The research the author discusses has nothing to do with Crossfit. The press release does, however, attempt to associate a high-fat diet (promoted by some Crossfitters as healthy than other diets) with lower incidence of cardiovascular disease by comparing incidence of disease between residents of Switzerland and Australian aboriginals living in modern Australia. The claim was that a high-fat dining Swiss have less cardiovascular disease than the presumed low-fat dining Australian Aboriginals and that, therefore, high-fat diets are healthier than low-fat diets.


I have not looked up the statistics for the Swiss, but Australian Aboriginals have been suffering increasing rates of cardiovascular disease over at least the last 30 years.  Few modern Aboriginals are likely to be following a traditional Aboriginal diet. It is extremely unlikely that the increasing rate of heart disease observed in Australian Aboriginals has been caused by low intake of dietary fat. Aboriginals are suffering from increasing obesity and diabetes just like so much of the rest of the world. The high incidence of cardiovascular disease in Aboriginals may be due to genetic factors and a change to a Western-type diet but extremely unlikely to be caused by a low-fat diet (especially since they are not eating this way anymore anyway).  There are also obviously many other differences between the Swiss and the Aboriginals (differences in poverty levels, availability of lederhosen and differences in other possibly important variables like intake of strong coffee and chocolate).




 Rowley K, Walker KZ, Cohen J, Jenkins AJ, O'Neal D, Su Q, Best JD, & O'Dea K (2003). Inflammation and vascular endothelial activation in an Aboriginal population: relationships to coronary disease risk factors and nutritional markers. The Medical journal of Australia, 178 (10), 495-500 PMID: 12741936 O'Dea K (1991). Westernisation, insulin resistance and diabetes in Australian aborigines. The Medical journal of Australia, 155 (4), 258-64 PMID: 1875844

Estrogen and Progesterone in Waterways

In the last post, I was speculating about how estrogens from effluent might end up in way water ways and end up increasing the incidence of prostate cancer. I wondered if the problem (if it there is anything more than a chance association) might be progesterone from birth control pills rather than estrogen. Progesterone is markedly non-soluble in water so it seemed unlikely at first thought. Poking around a little, progesterone might end up in sewage effluent after all. The three studies below report on fecal and/or urinary progesterone, conjugated progesterone or "progesterone metabolites" in animals. So . . . maybe progesterone contamination of water might be relevant. And, not all sewage is filtered and treated. I recently watched someone emptying a truckload of portapotties into one of our local creeks. (Yes, I called the police, who told me it was not their problem.) Don't know if anyone has looked at this or not. If you know, please have at it in comments.

deCatanzaro D, Muir C, Beaton EA, & Jetha M (2004). Non-invasive repeated measurement of urinary progesterone, 17beta-estradiol, and testosterone in developing, cycling, pregnant, and postpartum female mice. Steroids, 69 (10), 687-96 PMID: 15465115Kinoshita K, Inada S, Seki K, Sasaki A, Hama N, & Kusunoki H (2011). Long-term monitoring of fecal steroid hormones in female snow leopards (Panthera uncia) during pregnancy or pseudopregnancy. PloS one, 6 (5) PMID: 21559303Brown JL, Wasser SK, Wildt DE, & Graham LH (1994). Comparative aspects of steroid hormone metabolism and ovarian activity in felids, measured noninvasively in feces. Biology of reproduction, 51 (4), 776-86 PMID: 7819459google-site-verification: googleaa234ad89e44d776.html

Response to a friend on significance of Triclosan in drinking water

Sorry Friend. That was a poor response to your question about the significance of Triclosan following news of the chemical as an androgen blocker in water.

Triclosan is a thyroid disruptor and according to recent reports, an androgen blocker. As an anti-androgen, exposure could be important to male fetuses, since it could potentially interfere with development of the genito-urinary system, which could mean birth defects like hypospadias, small phallus, or non-obvious problems like changes in numbers and proportions of cells that would, later in life, produce sperm and testosterone. Thyoid inhibition has its own effects on development of the male reproductive system as well. So there might be some interesting interactive effects if both thyroid hormones and androgens are impacted. If that would occur you'd see reduced fertility. In an adult lowered testosterone would lead to other problems.

Blocking androgens, on the upside, might lead to less prostate cancer. It would be interesting to see if Dial Soap or other triclosan-containing products use this as a marketing point. "protects against body odor, gingivitis AND prostate cancer" Let's guess not.

Lastly, there was also an article out recently that associates rates of prostate cancer with presumed levels of estrogen (presumably from urine from women on birth control) in water supplies (Margel & Fleshner 2011). This was unexpected to me, until I thought about the pathway through which testosterone is produced. Testosterone can be synthesized from Progesterone, which is also present in birth control pills. So, it may be the progesterone, rather than estrogen, that is causing the problem. Progesterone is not water soluble, so its unlikely to be found in water systems unless conjugated to something else or incorporated in something else, so this is just speculation on my part.

Back to Triclosan. You can find some basic information on what kinds of products contain Triclosan at the Environmental Working Group Website. Its dated 2008, but the basic information may be useful.

For all of this, note that, for Triclosan, the picture is far from clear, as recent papers also report Triclosan enhancing androgenic activity in vitro (Christen et al. 2010) and as having estrogenic activity (Jung et al. 2011). Neither of those qualities is desirable in an environmental contaminant.
Best wishes,

Margel, D., & Fleshner, N. (2011). Oral contraceptive use is associated with prostate cancer: an ecological study BMJ Open, 1 (2) DOI: 10.1136/bmjopen-2011-000311

Christen V, Crettaz P, Oberli-Schrämmli A, & Fent K (2010). Some flame retardants and the antimicrobials triclosan and triclocarban enhance the androgenic activity in vitro. Chemosphere, 81 (10), 1245-52 PMID: 20943248

Jung EM, An BS, Choi KC, & Jeung EB (2011). Potential estrogenic activity of triclosan in the uterus of immature rats and rat pituitary GH3 cells. Toxicology letters PMID: 22062131

Rostkowski, P., Horwood, J., Shears, J., Lange, A., Oladapo, F., Besselink, H., Tyler, C., & Hill, E. (2011). Bioassay- directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. Environmental Science & Technology DOI: 10.1021/es202966c

Selenium, Brazil Nuts and Testosterone

There seems to be a lot out in the popular press or online material that incresing selenium intake will increase a healthy man's testosterone production (example and example II from Forbes Magazine: what were they thinking?), but little, if anything, in the scientific literature to support that idea. (I like the scientificky approach used by that website, especially the graph that shows no effect, and no indication of variability in the data points). However, elevated testosterone, long term, will increase risk of testicular and prostate cancer. There has also been recent emphasis on consumption of brazil nuts as a natural source of selenium that will boost testosterone and increase virility.

Selenium is protective against prostate cancer, and good for testicular development (fetal period . . . sorry guys) and possibly protective against other oxidative-stress-induced ailments, testicular or not. On the other hand, selenium, at high concentrations can result in DNA damage, and thus increase risk of cancer. The problem with supplementing, either through tablets, or through consumption of a natural product high in selenium, is that we do not know where the lines of good and evil cross.

As for Brazil nuts, selenium concentrations in any plant should be dependent on the concentration of selenium in the soil in which it grows, therefore, the concentration of selenium in Brazil nuts probably varies. This turns out to be the case, with nuts grown in Manaus-Belem more than ten times higher in selenium than those grown in Acre-Rondia. Someone consuming Brazil nuts may or may not be making a significant increase in selenium intake.
Chang, J. (1995). Selenium content of Brazil nuts from two geographic locations in Brazil Chemosphere, 30 (4), 801-802 DOI: 10.1016/0045-6535(94)00409-N

ATIF, F., YOUSUF, S., & AGRAWAL, S. (2008). Restraint stress-induced oxidative damage and its amelioration with selenium European Journal of Pharmacology, 600 (1-3), 59-63 DOI: 10.1016/j.ejphar.2008.09.029

Brozmanová J, Mániková D, Vlčková V, & Chovanec M (2010). Selenium: a double-edged sword for defense and offence in cancer. Archives of toxicology, 84 (12), 919-38 PMID: 20871980
Henderson, B. (2000). Hormonal carcinogenesis Carcinogenesis, 21 (3), 427-433 DOI: 10.1093/carcin/21.3.427

Schistosomiasis may be protective against Auto-Immune Disease

Following up here on the associations between parasite infection and reduced incidence of autoimmune diseases such as diabetes, thyroid disorders, arthritis and possibly asthma, this time with a specific focus on Schistosome infection. Schistosomias is a common infection in many areas of the developing world, and is thought to be the second most important human parasite after malaria. Infection may be sub-clinical with little or no indication of infection.

Osada et al. (2009) reported on lower inflammation and less arthritic response in infected mice. Arthritis can be induced in mice by injecting them with Collagen II. A recent publication by Xiao-Ping Chen's group (He et al. 2010) further report that the inhibitory effect of schistosomiasis is dependent on the life stage of the schistosomes. Schistosomes have a very complex life cycle and apparently some phases are more protective or induce different physiological responses in the host than others. Acute infection and egg-laying by the parasite are associated with less response to the collegen injections. Very interesting.

However, it is not advised that people run out and attempt to infect themselves, which can be pretty horrible and disfiguring. Malnutrition, anemia and lowered IQ have been observed in infected children, and increased incidence of bladder cancer is seen among infected adults. Still, it will be interesting to see where this work goes, and what treatments may be eventually developed. Thank you Osada et al. and He et al.

He, Y., Li, J., Zhuang, W., Yin, L., Chen, C., Li, J., Chi, F., Bai, Y., & Chen, X. (2010). The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent BMC Immunology, 11 (1) DOI: 10.1186/1471-2172-11-28

Araújo, M., Hoppe, B., Medeiros Jr, M., & Carvalho, E. (2004). Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases Memórias do Instituto Oswaldo Cruz, 99 DOI: 10.1590/S0074-02762004000900005

OSADA, Y., SHIMIZU, S., KUMAGAI, T., YAMADA, S., & KANAZAWA, T. (2009). Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators International Journal for Parasitology, 39 (4), 457-464 DOI: 10.1016/j.ijpara.2008.08.007