SOLUBLE UV SUNSCREEN FILTERS ARE A PRIMARY ROUTE OF EXPOSURE TO HORMONE DISRUPTORS

Hormone disruptors or Endocrine Disrupting Chemicals (EDCs) have been in the news again. At The Endocrine Society Meeting  (2016) , a Danish study (Skakkebaek et al) confirmed that 13/30 UV filters tested or 45%  had direct effects on human sperm cells explaining the male infertility associated with sunscreens. They imitated the hormones progesterone and prostaglandin, not estrogen, as is usual. They disrupted numerous functions required for fertility by simulating hormonal signals controlling the CatSper ion channel for calcium flux – a very specific mechanism for human sperm cells. Eight  of the 13 offending sunscreen agents are still used widely in N. America.

The response from the dermatology/industry alliance was swift and predictable. Many dermatologists appearing in the  media, are consultants for the sunscreen industry. A NYU dermatologist and consultant for Johnson & Johnson immediately proclaimed that this was not science, as it was done in a test tube. That is so absurd- many studies are done in vitro and there are already  numerous studies in vitro and in vivo in animals and humans that identify several UV-filters as endocrine disrupting chemicals. There is already enough science implicating hormone disruptors in human endocrine disorders that any human study would never be ethical. He also said that dermatologists must only pay attention to the “known science”. “The most important thing to remember is we do this experiment with tens of millions of people every summer [as they wear sunscreen on our beaches and outdoors], and we’re not seeing effects that would be predicted by a study like this.”  This is even more bizarre. As a physician, I am embarrassed at these ridiculous statements. These consumers are not being followed over a lifetime with semen analysis and epidemiologic studies looking for all the possible effects like fibroids, endometriosis, uterine cancer, breast cancer, diabetes, obesity, and several childhood disorders.  A definitive study would require  a large number of participants from pregnancy through childhood to adult ages- followed over a lifetime to see what the differences in reproductive and cancer outcomes were. Such a study is obviously impossible.

The Danish study also showed that the effect began at very low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens. It  provides a context and an explanation for a prior report from the National Institute of Health that men with high exposure to UV filters like oxybenzone had a 30 percent reduction in fecundity, the biological ability to reproduce. Lower fecundity may result in a longer time to pregnancy. “Our next step is to figure out how these particular chemicals may be affecting couple fecundity or time to pregnancy—whether it’s by diminishing sperm quality or inhibiting reproduction some other way.” said Germaine Louis, Ph.D., director of the Division of Intramural Population Health Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The data came from the Longitudinal Investigation of Fertility and the Environment (LIFE) study, established to examine relationships among fertility, lifestyle factors, and exposure to environmental chemicals.

Most dermatologists like the J&J consultant, are either unaware of, or choose to ignore  the WHO and Endocrine Society positions and the prior NIH report. 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, confirming how things have changed in just over a decade. In 2002 the scientific consensus was that there was only weak evidence for causal links existed but that careful study and observation was necessary.  Ten years later the WHO/UNEP report cite numerous examples of human and wildlife effects that call for focused action on this growing problem. “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.

For the past 10 years, I have urged physicians and patients to realize that sunscreens and cosmetics represent the major source of exposure to hormone disruptors for most urban dwellers in N. America. Consider my deductive but evidence based argument outlined below. I respectfully submit it is persuasive. Consider it in the context of the level of caution you exercise where the health of your children is concerned.

 Soluble UV filters definitely reach human blood, tissue, and regulatory brain centers through the skin

This is not theoretical as stated by dermatologists in The Globe and Mail newspaper. Basic science tells us that any fat soluble chemical with a molecular weight (MW) < 500 Daltons will pass through the skin very rapidly. The soluble filters still used in most sunscreens in this category include: avobenzone, oxybenzone (benzophenone), homosalate, octisalate, octocrylene, octinoxate (non-encapsulated), and 4-methyl benzilidene camphor (enzacamene).No study is needed  to tell me that all of these are more likely than not to enter our bodies, and reach the unborn at every stage of pregnancy. No study is needed to know that the entire group are hormone disruptors, based on the principle of isoform function, where chemicals with similar structure bind to the same endocrine receptor and produce the same effects. Since  oxybenzone and homosalate are proven hormone disruptors, so are avobenzone and octisalate. The Danish study (2016) on altered sperm function indicted all of the above plus a few others.

• 8 studies I know of  confirm  that UV filters of this type attain blood levels in humans, not from animal studies. They come from diverse populations in the USA, France, Denmark,  Switzerland, and Sweden. A few especially refute the propaganda from the dermatology/industry alliance:
• The CDC study from 2008 (Calafat et al) that showed 97% of 2517 Americans, age 6-70, of both genders had oxybenzone in their urine., and also found Bisphenol A (BPA) in 93.8% of these urine samples.
• An EU study from Krause et al (2012) showing that 85.2% of European mothers had various UV filters in breast milk . 100% of the breast milk samples had pesticide residues- persistent organochlor pollutants (POPs), i.e., organochlor pesticides and metabolites, polybrominated diphenylethers and polychlorinated biphenyls (PCBs). This tells us that human contamination is related to the route of exposure. Pesticides contaminate the environment, water, and our food chain. Everyone is susceptible in certain countries. Not everyone uses a cosmetic or a sunscreen – hence the lower rate of breast milk contamination.
• Zhang et al (2013) showed that benzophenones appear in paired urine and blood samples in adults , children, and pregnant women. Matched maternal and fetal cord blood showed that benzophenones crossed the placenta.

Hormone disruptors are definitely affecting the health of this and the next generation.

My wife, Dr. Sharyn Laughlin, and I at company event

I am married to dermatologist/ photobiologist Dr. Sharyn Laughlin (www.laserderm.ca). We share the concern of the WHO, the United Nations Environmental Program, The Endocrine Society, The European Pediatric Society, The European Commission and others, that hormone disruptors are now strongly linked to adverse reproductive outcomes, endocrine cancers, and neurological disorders like ADHD, possibly Autism Spectrum disorder, Parkinson’s disease and Alzheimer’s, asthma, obesity, and diabetes.

Consider the statement from a 2009 review from The Endocrine Society : 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.

Their recent warning (September 2015) is even more ominous:

• Unborn children are particularly at risk when exposed to endocrine disrupters, according to the society.
• The new statement corroborates earlier findings, linking endocrine disrupters — in addition to their impact on obesity and diabetes — to effects on male and female reproductive health, hormone-related cancers, prostate conditions, thyroid disorders, and neuro-developmental issues.
• Andrea Gore, PhD, Professor and Vacek Chair of Pharmacology at the University of Texas at Austin, and Chair of the Task Force that developed the statement, said the group is highlighting obesity and diabetes this time because the evidence for effects on these diseases is much stronger than it was 5 years ago. She advises that not just endocrinologists, but general practitioners, pediatricians, obstetrician-gynecologists, and fertility doctors should emphasize reduction of exposure to these disrupters when they talk to their patients.

 My comment:  Dr. Gore, like the WHO and others, has  also missed  that dermatologists and sunscreens are at epicenter of the problem. Given the patterns of exposure and the way EDCs intersect with our daily lives, sunscreen filters and cosmetic chemicals are the likely primary source of exposure for most of us in a developed society.

Why sunscreens and cosmetics are the main exposure to EDCs for most urban residents in N.America.

Over a 1000 chemicals are now identified as EDCs. Most have never been studied for their effects on humans. The ones that likely intersect with our lives include:

• Persistent organochlor pollutants (POPs) in pesticides and flame retardants in furnishings
• Bisphenol A (BPA) and phthalates in cans, plastics and the ink on some receipts
• Soluble sunscreen filters and cosmetics
• Metalloestrogens: aluminium, cadmium, antimony, selenium, tin, copper, lead, arsenite, nickel, copper, lead, cobalt, antimony, and arsenite
• Various phytoestrogens – flavones, soy, isoflavones, favonols

Many are weak and of less significance than pesticides and UV filters. Some contaminate our food and water supply. However, the principle of multiplication is an increasing issue where an individual may be exposed to several sources. Bisphenol A  (BPA) and phthalates in plastics and tins, and produce sprayed with pesticides are publicised as a source of human EDC exposure by ingestion. This exposure is more tangential 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 are the most important source of EDC exposure in a first world society.  They may be used one or more times daily in combinations of products, applied to a part of or the whole body, passing directly into the blood and brain. Soluble filters do require re-application every few hours for outdoor exposure and swimming. They wash off more easily and as they are absorbed into blood they require replacement on the skin. Particle type insoluble filters have no percutaneous entry and can be made into bioadhesive dispersions that may  not require re-application.

Linda Marsi in the October 2015 issue of MORE magazine and experts like Dr. Gore talk about reducing your exposure by avoiding storage or microwaving food in plastic containers with known EDCs, not handling receipts where ink contains phthalates, avoiding household exposures from flame retardants and stain or water repellants. Every precaution is worthwhile, but these are mostly low level and extraneous sources. Any benefit  from these precautions are negated if you ignore the greater exposure that comes from applying a cosmetic or sunscreen to large areas of skin. Many experts warn about avoiding EDCs but the silence on EDC exposure from soluble sunscreen filters is deafening:

• After the NIH reported the data from the LIFE study on the link between infertility and benzophenone type sunscreens, infertility experts expressed concern that BPA and phthalates are a concern to all couples wishing to conceive, with the caveat that the growing body of evidence that EDCs adversely affected reproductive capacity was  “ preliminary”. Dr. Ruth Lathi, a researcher and director of Stanford’s Recurrent Pregnancy Loss Program and Dr. Linda Giudice, president of the American Society for Reproductive Medicine and a professor of reproductive sciences at the University of California at San Francisco recommended the half-measures that couples wishing to conceive should not store or microwave food in plastic containers with BPA.
• Germaine Louis , Ph.D., director of the Division of Intramural Population Health Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development was involved with the LIFE study. She said “Our next step is to figure out how these particular chemicals may be affecting couple fecundity or time to pregnancy—whether it’s by diminishing sperm quality or inhibiting reproduction some other way.” Dr. David Adamson, founder and CEO of Advanced Reproductive Care, Inc. (ARC), the largest network of fertility specialists in the United States and a pioneer in reproductive medicine joined Dr. Louis in advising that  men concerned about fertility should reduce their use of benzophenone UV filters—and  by washing after returning indoors.

The analysis and advice in these statements is incomplete. I repeat that no one, including couples hoping to have a child, needs to moderate their use of sunscreens. The proper advice is to avoid all soluble filters. Everyone should use sunscreens with safe insoluble particle based filters that actually provide better balanced UV attenuation with higher UVA protection. Washing off benzophenone or any soluble filter at the end of the day is ineffective and illogical. Absorption is rapid, peaking  at about 10% of the applied amount, 1-2 hours after each application. If  tangential exposure from BPA and phthalates in cans and plastics pose a level of exposure to be considered, then  daily recurrent exposure from soluble UV filters and cosmetics is a greater concern. Most city dwellers in N. America have little if any exposure to pesticides, unlike the third world where indiscriminate pesticide use may explain higher rates for precocious or early puberty in girls as young as age 6-7.

My Final Thoughts

The WHO, UNEP, European Commission, European Pediatric Society, The European Environmental Agency, The Endocrine Society and The Pediatric Endocrine Society USA based), all agree 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:

1. In Females- uterine fibroids, endometriosis, uterine and breast cancer, infertility, polycystic ovarian syndrome (PCOS), precocious puberty, and premature menopause.
2. In Males: prostate cancer, feminization syndromes (testicular dysgenesis).
3. In children: asthma, learning/behaviour disorders (ADHD, autism spectrum disorder).
4. In both genders: thyroid cancer, type 2 diabetes, obesity, cardiovascular disease, Alzheimer and Parkinson disease.

The dermatology/industry alliance cites irrelevant studies that the toxic doses in rats or mice would not ordinarily be attained in humans from the usual pattern of everyday use. The Danish researchers (Skakkebaek et al) in their 2016 study, found that 13, or 45 percent, of the 29 UV filters tested induced calcium ion influxes in the sperm cells, thus interfering with normal sperm cell function. “This effect began at very low doses of the chemicals, below the levels of some UV filters found in people after whole-body application of sunscreens said. Some studies in animals do suggest that UV filters are not harmful. It is difficult to prove a negative. What is needed is proof that they are safe in humans, as we are not large rodents. 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).  This is not a perfect study but consider if it should be ignored because a study on uterine weight in mice suggested no hormonal effects from UV filters. Most of the data from animal studies suggest that UV filters affect a variety of reproductive and other hormones. The most blatant flaw in the industry disingenuous position is that endocrine receptor function in humans is different from lower animals. Consider the potential effects on a 10-week old human embryo from even a few hormone disruptors binding to even a few receptors. The effects at this critical period of human development on endocrine function and imprinting, or on neural signaling mechanisms that are hormone sensitive, could be very profound and usually permanent.

 The developing fetus and young or pubescent children are the most vulnerable humans, since infinitesimally low or undetectable, indeed any level of exposure may cause hormonal reproductive defects, particularly at these critical times of development. The existing animal model data and human evidencetaken together, suggest that exposure to EDCs during these critical times plays a role in the increased incidences of the human diseases listed above. The definitive human study over a lifetime can never be done, given the complexity imposed by varying effects due to different ages at exposure, a latent period that could be 20-50 years, multiplication from exposure to several EDCs, transgenerational  effects through altered enzymes that affect genes, confounding factors like other causes of these diseases, and the ethical dilemma since there is already strong evidence of adverse effects. We believe in The Precautionary Principle, as mandated under Canadian law, to err on the side of caution, since it meets our personal approach to medical practice and the first precept in medicine- primum non nocere or “first do no harm”. Physicians have a duty of care to advise patients that soluble filters enter blood, particularly in pregnancy, just as they do for any medication, even aspirin. Every expectant or nursing mother and parent, deserves to make their own informed choice:

• Either: use a sunscreen with filters and chemicals that give incomplete protection, contaminate your body, and are strongly linked to serious permanent disorders, other temporary problems like photocontact allergy in humans, are harmful to lower species and damage the coral reefs as they wash off swimmers.
• Or: exercise an abundance of caution or the precautionary approach by selecting a sunscreen with filters that remain on the skin, give arguably better or balanced protection, never attain blood, fetal, or brain levels, and have no risk for even minor adverse effects like photocontact allergy, or pose any risk to animals or the environment.

As a former obstetrician, I appreciate the persuasive simplicity that anything safe to use in pregnancy is safe to use for everyone. Dr. Laughlin describes an effective sunscreen as one that actually prevents skin cancer and photoaging. Coming from Maternal Fetal Medicine, I define a safe sunscreen as one that is safe to use in pregnancy. Soluble filters operate almost exclusively in the UVB and shortwave UVA2 wavelengths. Only avobenzone has any UVA1 attenuation. The usual combination of soluble filters provide a potent mix of hormone disruptors while providing UVB-biased protection that hardly lowers the risk of skin cancer and photoaging- mediated mostly by UVA1. Rising cancer rates are related to these UVB-biased sunscreens that dominate the N. American market. Particle based sunscreens with zinc oxide alone, or with titanium dioxide or encapsulated octinoxate meet both objectives- safety and efficacy. It is ironic that the sunscreens with soluble filters have limited benefits while probably exposing you to harm. The prudent choice seems rather obvious, but most consumers are never given the relevant information. Physicians have a duty of care to advise you that soluble filters enter your blood, particularly if you are pregnant or the parent of young or pubescent children.

The Precautionary Principle 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 at the FDA and Health Canada, often 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 in pregnant women and children. This shifts the burden of protection against harm through caution, from the government to you. BPA was justifiably banned under The Precautionary Principle as a carcinogen and hormone disruptor. I believe The Precautionary Principle is being ignored where soluble sunscreen filters are concerned. The case for banning them is much stronger than that of BPA.

Can Using a Sunscreen Be Worse than Using a Tanning Bed? The Health Implications of a UVB Biased Sunscreen.

The New Study that Shows How a UVB Sunscreen Can Be Worse than a Tanning Bed

The Role of Long Wave UVA in Skin Cancer

There is an unrelenting rise in skin cancer rates in North America with an annual increase around 2-3 % over the past 3 decades. In the UK there was an alarming increase of 40% in the past 4 years. Empirical analysis of global skin cancer rates suggest that rates are levelling off or decreasing in countries with higher UVA-Protection Factor (UVA-PF) levels in sunscreens (2015 Sunscreen Symposium, Florida, September 2015). The compelling evidence for the primary role of UVA - particularly the UVA1 or longwave UVA -  in the genesis of skin cancer – comes from a number of scientific studies over the past 15 years (Halliday 2002, Agar 2004, Noonan 2012, Rünger 2012). This is logical and intuitive as UVA is more abundant than UVB and penetrates deeper into the skin.

The primary objectives of photoprotection  must be to prevent rising rates for skin cancer, reduce health care expenditures for a disease with potentially preventable aspects, and to reduce other effects of UV radiation, like photoaging and immune suppression. The continual 2-3% annual rise in skin cancer rates for North America shows that the current approach has failed. Critical analysis argues that ineffective UVB biased sunscreens are an important contributory factor. Cancer prevention and immune protection  from sunscreens in humans is dependent on protection from UVA and cannot be predicted from the SPF (sun protection factor), more a measure of UVB attenuation.

There is  a logical and evidence-based argument that the exclusive use of balanced sunscreens, which provide spectral homeostasis or uniform protection at every wavelength can reduce cancer rates and photoaging. The current  science confirms that UVB causes direct DNA damage, whereas UVA results in direct DNA damage and indirect effects from ROS (reactive oxygen species), photoimmunosuppression, and disruption of repair mechanisms.  UVB initiates and modulates the damage cycle but UV (particularly UVA1) completes the process. Photoprotection with traditional UVB biased sunscreens with little or no UVA protection must now be abandoned and a new clinical strategy adopted by doctors and as a public health policy.

How Can A UVB Biased Sunscreen Do More Harm than Good?

There is another powerful bit of evidence that implicates the widespread use of UVB-biased sunscreens, with little or no UVA1 protection, in rising skin cancer rates and visible photoaging at younger ages. Daily use of UVB biased sunscreens that dominate the market, exposes the patient to asymmetric UVA1 radiation, similar to a tanning bed. More people develop skin cancer because of tanning than develop lung cancer because of smoking. One indoor UV tanning session increases users’ risk of developing squamous cell carcinoma by 67 percent and basal cell carcinoma by 29 percent. People who first use a tanning bed before age 35 increase their risk for melanoma by 75 percent.  

There is an important  parallel between the asymmetric UVA1 from tanning bed exposure and using a UVB-biased sunscreen, either on vacation or every day. This crucial fact escapes our regulators, most physicians including dermatologists, and the cosmetic industry. 

Vacation exposure over 2 weeks with typical sunscreens for protection could be double the radiation received from 10  eight minute tanning bed exposures. In extreme cases of recreational sun exposure where sunscreens providing suboptimal broad-spectrum protection are used, the UV insult to the skin is likely to result in higher cumulative exposures than commonly employed sunbed practices (Diffey et al).

This occurred to me several years ago but the science and physics was beyond my capability. I kept asking Uli Osterwalder- one of the authors in the study and a friend- about this obvious concern, until they finally did the calculations. It is a computer derived analysis that suggests the wrong sunscreen - UVB-biased - may be more dangerous than tanning bed exposure. Both provide asymmetric UVA radiation to your skin. There is another cautionary aspect to this. The vacation model is more acute and intense but what about everyday exposure if using a UVB-biased sunscreen? Many outdoor occupations reach or exceed the vacation exposure.

If tanning beds cause higher risks for skin cancer, then providing a patient with a UVB biased sunscreen that gives a similar UV radiation profile, relative to the right conditions of exposure and time, should also be considered as an undesirable measure. For doctors involved with rejuvenation, prescribing a balanced sunscreen that gives adequate UVA1 protection is a responsible practice standard. This is an integral part of post treatment care after rejuvenation procedures. Without balanced protection, the patient resumes accelerated photoaging from UVA1 exposure and the  treatment benefit is quickly lost. Repeat treatments will then be required more quickly. 

What Is A Better Alternative?

Adequate but safe UVA1 protection is only attainable with filters like zinc oxide (>20%), zinc oxide (>15%) plus 7.5% titanium dioxide or encapsulated octinoxate, bemotrizinol, and bisoctrizole – insoluble particle type filters with no entry into our bodies. Regrettably,  the last two safe and highly effective insoluble particle filters, have yet to be approved by Health Canada and the FDA, despite their global use in every other country over the past 15 years.

Most UVB-biased sunscreens use the soluble filters that penetrate skin into blood and even tissues like receptors in the brain. The group includes oxybenzone (benzophenone), homosalate, octisalate, octocrylene, non-encapsulated or regular octinoxate, and 4-methyl benzilidene camphor. They are more active in UVB and shortwave UVA (UVA2). Some UVA1 activity comes from avobenzone, another soluble filter that obtains tissue levels. It enters the body and is unstable in sunlight. Most parents and pregnant women are unaware that these filters (used in over 80% of our sunscreens) gain entry to our bodies, reason enough to avoid them.

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. Oxybenzone and its structural cousin avobenzone are now the leading causes of photocontact allergy (Warshaw 2012). A 2015 report (Downs et al) confirms other studies over the past decade that oxybenzone washing of sea-bathers is genotoxic, kills larvae of reproducing coral, and converts the planula from a motile to a sessile state by ossification. Oxybenzone found in 65% of our poses a hazard to coral reef conservation and threatens the resiliency of coral reefs to climate change.

Recommendations for Practitioners and Consumers:

You are faced with a simple choice in selecting a safe and effective sunscreen:

·       UVB- biased products with tiny soluble organic filters that give incomplete protection (inadequate UVA1 protection) and are implicated with adverse effects on our health and the environment. They are likely a root cause of rising cancer rates and early photoaging.

·       A balanced or truly broad spectrum sunscreen using insoluble filters, large particles that remain on the skin, have no known adverse effects on human health or the environment, and give you better protection, where the right combination can approach that of textiles and staying out of the sun.

·      Balanced sunscreens using insoluble particle type UV filters with no entry into blood of mother or fetus are safe to use in pregnancy. More egregious to me, is the fact that nearly all physicians fail to advise pregnant women and parents about percutaneous absorption of soluble filters and their possible hormone disrupting and carcinogenic effects. As a former obstetrician, I appreciate the persuasive simplicity that anything safe to use in pregnancy is safe to use for everyone.

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