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.