A Public Health Perspective on Endocrine Disrupting Chemicals

Moving Forward: How Should We Deal with EDC’s

Some Current Flaws in the EDC Debate

In considering the problem there are important principles of human endocrine receptor function that provide a perspective and negate all animal studies referred to by industry and Health Canada. Several aspects of human endocrine receptor physiology seem to escape regulators like the FDA or Health Canada, the sunscreen industry, and unfortunately most dermatologists. They are either unwilling or unable to understand basic concepts even when the World Health Organization (WHO), The Endocrine Society, and The United Nations Environmental Program, have gone to great lengths to alert the world to the science, and the rising incidence of reproductive disorders and cancers in humans and lower species. Important aspects of human endocrine receptor function  provide a perspective (taken from WHO/UNEP ES 2012). Humans are not large rodents and human endocrine receptors function differently from mice and other lower species. Animal studies in mice and other lower species suggest that only large doses are toxic.

In humans the age of exposure is critical, and endocrinologists  now use the terminology “the developmental basis of adult disease.”  I also believe that puberty represents another period of increased vulnerability for obvious reasons. There may be a delay before the consequences are evident in adult life or later on. Furthermore, effects of different classes of EDCs may be additive or even synergistic. In humans, infinitesimally low levels of exposure— indeed, any level of exposure at all—may cause endocrine or reproductive abnormalities, particularly if exposure occurs during a critical developmental window. Surprisingly, low doses may even exert more potent effects than higher doses. EDCs may exert non-traditional dose-response curves, such as inverted-U or U-shaped curves.

Both of these concepts have been known for hormone and neurotransmitter actions, but only in the past decade have they begun to be appreciated for EDCs, which may also affect not only the exposed individual but also their children and subsequent generations. Recent evidence suggests that the mechanism of transmission may in some cases involve the germline  and may be nongenomic.  In other words, effects may be transmitted not due to mutation of the DNA sequence but rather through modifications to factors that regulate gene expression such as DNA methylation and histone acetylation.

Bisphenol A (BPA) and phthalates in plastics and tins are publicized as a source of human EDC exposure mainly by ingestion. This exposure is more tangential and incidental than sunscreen or cosmetic chemicals. The liver may metabolize and ameliorate the effects of EDCs ingested. Sunscreen chemicals absorbed through the skin obtain direct access to tissues and the brain and bypass this protective mechanism. Logical and critical thinking leads you to the unavoidable conclusion that sunscreen and cosmetic chemicals, often used on a daily basis and in combinations of products, which pass into the blood and brain, are the most important source of EDC exposure in a first world society.

How Should We Approach the Issue?
Physicians subscribe to the principle of “First do no harm” and should believe in The Precautionary Principle. It considers the limits of science and errs on the side of caution, so that action in the public interest is not delayed until the damage is done. Regulators in N. America, unlike those in Europe, seem to act only when there is incontrovertible evidence of harm, which is too late. This policy is illogical since it is criminal or unethical to do definitive studies on humans, particularly pregnant women and children. The follow-up phase would have to span a lifetime to detect effects like cancer. We believe in the Precautionary Principle and that like BPA, we have passed the point where action is necessary with respect to soluble sunscreen filters. The Industry and regulatory regime response that animal studies show no evidence that sunscreen chemicals which attain blood levels do harm is simplistic. They do not provide evidence that these chemicals are safe. Extrapolations from animal studies are largely irrelevant to the human condition. It is ironic that the soluble filters that pose a risk to human endocrine function also give UVB-biased protection, and indirectly increase the risk of cancer and photo-aging in fair skinned individuals. Conversely, insoluble particle based filters pose no risk to humans and give balanced protection that reduces the risk of cancer and photo-aging.  It is time to counsel pregnant women about the risks of soluble filters and have them make an informed choice. Infertility specialists also need to pay attention. The entire population should make their own enlightened choice between soluble and insoluble filters.

The Application of the Precautionary Principle
These excerpts from essays by Marion Nestle and CHEM Trust are helpful. The application of “precaution”, “the precautionary principle” or “the precautionary approach” recognizes that the absence of full scientific certainty shall not be used as a reason for postponing decisions where there is a risk of serious or irreversible harm.

“The application of precaution is distinctive within science-based risk management and is characterized by three basic tenets: the need for a decision, a risk of serious or irreversible harm and a lack of full scientific certainty. It is enshrined in Canadian Law repeated in numerous legislation where required to protect human health and the environment. In the administration of Food & Drugs, it is mandated that when there is a concern for human safety, however minimal, it is necessary to err on the side of caution. In this respect Bisphenol A has been banned for use in plastic containers. European countries tend to subscribe to the precautionary principle.  Sweden, for example, has also banned BPA. The precautionary principle is one of the guiding principles of current EU policy making. The precautionary principle requires all the available scientific evidence to be taken into account, including all its related complexities, contradictions and gaps which need to be considered when trying to avert serious and irreversible damage to the population.

The precautionary principle takes the limits of science into the equation and tries to ensure that action is not delayed until the damage is done (and confirmed). To say the precautionary principle is unscientific misses the point, because all available scientific information is taken into account. The precautionary principle permits decision makers to take decisions in the absence of scientific certainty if there is a sufficiently serious risk. So it requires the exercise of judgement, in other words it is a principle of policy making. It is often impossible to design and implement experiments that prove that EDCs cause the increase in diseases that we are seeing. For example, this could require exposing pregnant women to chemicals and following their children for several decades to monitor the effects. However, if there are indications from tests on cell lines as well as animal experiments that chemicals have endocrine disrupting properties, we need to act before waiting for absolute proof of harm in humans. In my opinion, where EDC effects are concerned we are already too late.

A meaningful precautionary approach requires transparency in all assessments and their underlying scenarios. These assessments should look widely at exposure routes, otherwise small-scale measures may be decided instead of more effective wide-ranging policy responses, which protect those most vulnerable. For example in the USA, the limited BPA ban in baby bottles by the FDA, left pregnant women and the unborn child at risk from all other sources of exposure to BPA. The FDA still advises  that parents should examine bottles and discard them if worn or scratched because scratches can both harbor germs and, in BPA-containing bottles, lead to greater release of BPA.  For those who want to use baby bottles and feeding cups not made with BPA, consumers should know that such products are now widely available in the U.S. market. What all this means is that the FDA is sticking to—or has to stick to—a science-based position on BPA, but it is hedging bets by urging parents and the public to apply the precautionary principle and avoid BPA whenever possible.”

Some Conclusions

This shifts the burden of protection against harm from the government to you. I believe The Precautionary Principle under Canadian Law is being ignored where soluble sunscreen filters are concerned. The case for banning them is much stronger than BPA.  We know now about how the chemical oxybenzone in sunscreen can damage to reefs, but most of us still ignore the science that soluble UV filters (benzophenone and others) are human and environmental toxins. The pharmaceutical companies, the cosmetic industry, regulators, and most physicians, continue to ignore the persuasive evidence and breach The Precautionary Principle.   

Fetal and early childhood exposure (the developmental basis of adult disease) explains the genesis of numerous endocrine disorders and the cancers linked to hormone disruptors. Puberty is another time for concern but adults and seniors should not be dismissive of the jeopardy. There are links to Alzheimer’s and Parkinson’s for those EDCs that bind to certain receptors or affect neurotransmitter functions in the brain. Fetal and early childhood  exposures are linked to metabolic syndrome, obesity, and Type 2 Diabetes later in life. Metabolic systems that control  weight and glucose levels are affected, but even adult exposure may affect your chances of becoming obese or diabetic. Gru¨n and Blumberg  have named molecules that affect normal lipid metabolism adversely to promote obesity as obesogens. Hormone disruptors are among these obesogens that increase  the storage of fat. Exposure to EDCs may reduce the chance of success if you are an adult trying to lose weight. 

I have expressed my concern about EDCs for almost a decade but few physicians are listening. Those providing care around pregnancy should  counsel patients about sunscreens with filters that attain blood levels in mother and fetus, as they would for many  medications. I am slowly being vindicated. The WHO, The United Nations Environmental Program, The European Pediatric Society, The Endocrine Society, and others issued a warning in 2012 that there is strong evidence that EDCs are affecting human health. The NIH recently described links to male infertility for the benzophenone group. Facts about hormone disruptors are slowly filtering through to mainstream media. A good review by Linda Marsa appeared in the October issue of MORE magazine. Missing is the deductive conclusion that sunscreen chemicals are the most likely way in which hormone disruptors intersect with our daily lives, given the patterns of exposure in a first world society. The European Court of Justice recently ruled in a case brought by Sweden (on behalf of the Nordic countries) that the European Commission – tasked with oversight like the FDA or Health Canada - had "unlawfully refrained from laying down rules" to identify and ban endocrine disrupting chemicals. Health Canada and the FDA hardly even discuss this issue let alone recognise there is legitimate concern over human effects. If there is a ban of benzophenone – over 65% of sunscreens globally will have to be removed from the market. A growing number of consumers are already consciously avoiding it and other soluble filters.                                                                    

© Denis K. Dudley MD 2015

9 Reasons Why Oxybenzone Might be One of the Most Dangerous Chemicals in Your House

As a former specialist in Maternal Fetal Medicine (MFM) and Reproductive Endocrinology, I believe the Endocrine Disrupting Chemicals (EDC’s) are already affecting human health and I stopped exposing my family some 30 years ago. Even if they were not harmful, soluble filters gain entry to blood, tissue and brain. In pregnancy they pass through the placenta and bind to the various hormone receptors in the embryo and fetus. This is a bad idea. The World Health Organization report confirms the serious threat that hormone receptors pose to humans and wildlife. What it does not say is the obvious corollary that in our society, soluble sunscreen filters and other small Molecular Weight (MW) sized chemicals smaller than 500 Daltons, like the preservative parabens, are the single most important source of exposure to EDCs.

  

Sunscreens and their role in our Health

Although hormone disruptors are affecting human reproductive and other endocrine systems, there is a simple way to avoid a major source of EDCs.   There is also a simple way to protect this and the next generation from rising skin cancer rates. 

There is a growing list of adverse effects linked to hormone disruptors that must include the soluble sunscreen filters – oxybenzone, avobenzone, homosalate, octisalate, octocrylene and others. 

Some of these adverse effects include the following reproductive disorders: 

• infertility
• polycystic ovarian syndrome
• endometriosis
• fibroids
• breast and uterine cancer
• prostate cancer
• oligospermia 
• male infertility

Non-reproductive disorders include:

• ADHD
• asthma
• Parkinson’s 
• Alzheimer’s
•  thyroid cancer

Each person should make their own choice between two classes of sunscreens. Either use a sunscreen with small molecular weight (MW) soluble filters less than 500 Daltons. They are absorbed through the skin to reach blood, tissue, and bind to some receptors in the brain. They also give incomplete or UVB-biased protection that may prevent sunburn but affords little (if any) protection against skin cancer and photo-aging, where UVA1 rays play the major role. Lack of efficacy is compounded by the risk of serious and often permanent adverse effects, due to hormone disruption and carcinogenicity. 

Alternatively, you can choose a balanced sunscreen with insoluble particle type filters with  a MW greater than 500 Daltons.  This prevents entry into the skin as the filter remains within the outer dead layer of skin. A short list of UV Filters meet this criteria: zinc oxide, titanium dioxide, encapsulated octinoxate, Mexoryl SX™, Tinosorb S™, Tinosorb M™, Parsol SLX™, iscotrizinol, octyl triazone, and bisdisulizole disodium.  Only the first 3 are readily available in North America. Often formulas with a good filter are ruined by use of a soluble filter. These particles give more UVA1 protection with balanced UVB/UVA or better protection, and have no possible adverse effects. A balanced sunscreen can lower your melanoma and non- melanoma skin cancer risk and is the best anti-aging measure.

It defies any sensible logic that a parent or expectant mother would select soluble filters if they knew that they attain blood levels and reach the fetus. It is perplexing to me that many physicians continue to recommend their use. Even industry and regulators cannot deny that they attain blood levels. They use the absurd defence that only a small amount is absorbed. No comfort for a small child or unborn fetus. They also ignore the critical fact that these organic compounds are fat soluble and will bioaccumulate in tissue. These filters also come with the instruction to re-apply them several times per day- this can only add to their bioaccumulation in our bodies. 

The Oxybenzone Black List

Benzophenone, otherwise known as oxybenzone, gives context to how the danger exists in our everyday lives. Here is an evidentiary blacklist of reasons why this chemical should be banned from personal care products:

#1: It's Ubiquitous

A 2008 CDC study showed that this chemical is found in 97% of Americans tested, both genders between age 6-70 years (Calafat 2008).  It is still used in 65% of sunscreens in N. America and in over 950 cosmetics, which may explain why it is so pervasive. Women and girls had higher levels of oxybenzone in their bodies than males likely due to differences in use of body care products including sunscreens.

 #2  It's In Our Bodies and Our Children's Bodies

Other studies confirm the CDC report on this insidious and alarming  concern that this  chemical absorbs through the skin in significant amounts. A previous biomonitoring study reported that 96% of 6 to 8 year old girls had detectable amounts of oxybenzone in their urine (Wolff 2007). An earlier study detected oxybenzone in the urine of all 30 adult participants (Ye 2005).

#3 We Absorb More than You Would Think

Studies on human volunteers indicate a wide variation in the level of oxybenzone absorbed into the body, with some individuals absorbing at least 9% of the applied dose, as measured in excretions in urine (Hayden 1997; Janjua 2004; Sarveiya 2004; Gonzalez 2006). Volunteers continued to excrete oxybenzone many days after the last application of the chemical, an indication of its tendency to accumulate in fatty tissues in the body (Gonzalez 2006).

#4 It Increases Absorption Rates of Other Potential EDC's

In addition to its ability to absorb into the body, oxybenzone is also a penetration enhancer, meaning it's a chemical that helps other chemicals penetrate the skin (Pont 2004).

#5 It Has Potential Safety Concerns for Pregnant Women

Mothers with high levels of oxybenzone in their bodies were more likely to give birth to underweight or small for gestational age baby girls (Wolff 2008).

#6 It Could Be Affecting Our Fertility

It was also cited in a NIH report last year as being an important factor in male infertility, according to a study by the National Institutes of Health and the New York state Department of Health’s Wadsworth Center. This study merely underscores what the Endocrine Society, The WHO and The United Nations Environmental Program, have been saying for a decade- that the entire group of about 1000 known hormone disruptors have adverse effects on human reproduction, along with other effects on endocrine function and neural signalling. None of these reports follow through with the deductive analysis that given the patterns of human exposure, it is likely that soluble UV filters represent the most important source of EDC exposure in a developed society. 

#7 It's a Potential Carcinogen 

Sunlight also causes oxybenzone to form free radical chemicals that may be linked to cell damage, according to 2 of 3 studies (Allen 1996; Serpone 2002; Hanson 2006). Hence this generation of reactive oxygen species (ROS) could be carcinogenic to skin- this filter could be involved with causing the cancer it is supposed to prevent.

#8 It has Environmental Effects

The Hawaiians Knew- Sign from 2001 from beach in Maui, Hawaii 

Oxybenzone is contaminating  marine environments – washing off swimmers and in  municipal, residential, and wastewater effluent from marine vessels. A 2015 report (Downs et al) confirms other studies over the past decade that oxybenzone is genotoxic, kills larvae of reproducing coral, and converts the planula from a motile to a sessile state by ossification, due to its action as a skeletal hormone disruptor. Coral reef contamination of oxybenzone in the U.S. Virgin Islands ranged from 75 µg/L to 1.4 mg/L, whereas Hawaiian sites were contaminated between 0.8 and 19.2 µg/L.  Oxybenzone poses a hazard to coral reef conservation and threatens the resiliency of coral reefs to climate change.

#9 It's an Allergen

Oxybenzone and its structural cousin avobenzone are now the leading causes of photocontact allergy (Warshaw 2012). Although this is an infrequent problem, it is just one more reason why this chemical should be banned from personal care products. Consumers and physicians should question its continued use.  In most cosmetics, it’s only used to prevent discolouration in the product. It is still used in over 950 cosmetics and sunscreens.

Are All Sunscreen Actives Created Equally?

All of the organic soluble filters with small molecules (MW in the 250-500 Dalton range or < 1 nm)  should be viewed with the same concern . Many physicians still spread the myth that nanoscale zinc oxide usually 70- 300 nm and titanium dioxide 20-140 nm are so small they should concern us. In the world of sunscreens nano is large – usually  40-600 X larger than the soluble filter group, and nanoscale or micronized particles never penetrate beyond the outer layer of skin. There is a principle in endocrinology – isoform function – whereby chemicals with the same structure likely bind to the same hormone receptor and generally have the same effects. Hence avobenzone and octisalate very likely exert the same toxic effects as oxybenzone and homosalate, known to be hormone disruptors.  Why would anyone defend their  continued use? They enter the blood and brain of any person , including the most vulnerable – the unborn fetus and young children. They give you incomplete protection that could be a factor in rising skin cancer rates, and there is ample evidence that they are hormone disruptors and carcinogens in some cases. Finally, there is the evidence they also affect the health of lower species and destroy our reefs.

The WHO published a 250 page evidence based review entitled “ State of the Science of ENDOCRINE DISRUPTING CHEMICALS 2012 “ representing a broad scientific consensus among the leading experts in related fields. This echoes the warnings in scientific reviews  from The Endocrine Society,  The European Commission and the European Environment Agency. These documents implicate EDCs as a concern to public and wildlife health. In addition, the European Society for Paediatric Endocrinology and the Pediatric Endocrine Society have put forward a consensus statement calling for action regarding endocrine disruptors and their effects. “Of special concern are effects on early development of both humans and wildlife, as these effects are often irreversible and may not become evident until later in life.  The Endocrine Society stated : The evidence for adverse reproductive outcomes (infertility, cancers, malformations) from exposure to endocrine disrupting chemicals is strong, and there is mounting evidence for effects on other endocrine systems, including thyroid, neuroendocrine, obesity and metabolism, and insulin and glucose homeostasis.

The WHO list about 800 possible hormone disruptors, most of whom have never been studied for their possible human effects. Avoiding exposure to the extent you can is important in protecting our children and their children. 

As a follow up, my daughter Sara recently posted a reasoned discussion on why all consumers need to be concerned about hormone disruptors on our company blog (click here to read). She presented a persuasive argument on why a prudent person would try to reduce their exposure to these chemicals that now intersect with our daily lives. She is a new mother, and I take comfort from knowing that our precious new person will have little or no exposure to the permanent, serious, and even transgenerational adverse effects of these chemicals. As parents and grandparents, we will be vigilant and do our utmost to prevent her having any exposure.  She also blogged about sunscreen use in her pregnancy (click here to read).