special issue environmental medicine · special issue environmental medicine september 2015...

SPECIAL ISSUE

Environmental Medicine

SEPTEMBER 2015 SUPPLEMENT

Air Pollution, Disease, and Mortality

Toxic Metal Exposure: Interview With Robin Bernhoft, MD, FACS

BPA in Pregnant Women

Pregnancy Complications in Manicurists

Low-dose Chemical Mixtures as Carcinogens

Air Pollution Aggravates Diabetes

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SPECIAL ISSUE ENVIRONMENTAL MEDICINESEPTEMBER 2015 VOL 7, NO. 91 (SUPPL)

Contents

Copyright © 2014 by the Natural Medicine Journal. All rights reserved.

PEER-REVIEWED ARTICLE

6 Air Pollution, Disease, and Mortality

SPONSORED PODCAST

16 Exploring Bio-detoxification With Russell Jaffe, MD, PhD AUDIO INTERVIEW

17 Health Implications of Toxic Metal Exposure With Robin Bernhoft, MD, FACS

ABSTRACTS & COMMENTARY

18 Does Air Pollution Make Women Anxious?

20 Bisphenol A and Pregnant Women

22 Are Cosmetologists and Manicurists at Greater Risk for Pregnancy Complications?

27 Low-dose Chemical Mixtures as Carcinogens

29 Air Pollution Aggravates Diabetes

4 ©2015 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, SEPTEMBER 2015 SUPPLEMENT—VOL. 7, NO. 91 (SUPPL)

WALTER J. CRINNION, ND, received his doctorate in naturopathic medicine from Bastyr University, Seattle, Washington, in their first graduating class. Crinnion has been on the board of directors of the American Associa-tion of Naturopathic Physicians and has twice received their award for in-office research. He has been a faculty member

at Bastyr University; the National College of Naturopathic Medicine, Portland, Oregon; the University of Bridge-port School of Naturopathic Medicine, Connecticut; and Southwest College of Naturopathic Medicine, Tempe, Arizona, where he chaired the environmental medicine department. He is now the chief science officer at Enzy-medica, Venice, Florida.

ANNE MARIE FINE, NMD, gradu-ated from the Southwest College of Naturopathic Medicine (SCNM), Tempe, Arizona, and now practices in Newport Beach, California. She has completed the postgraduate certification course in environmental medicine through SCNM. Fine serves on the board of directors of the Naturopathic Association of Environ-

mental Medicine. She has published numerous articles in peer-reviewed journals and lectures frequently in the area of epigenetics and environment. She is also the founder and chief executive officer of Fine Natural Products, LLC, a company dedicated to formulating clean and nontoxic skin care products.

JULIANNE FORBES, ND, attended the State University of New York at Oneonta where she studied chem-istry and business economics and the University of New Hampshire where she obtained a master’s degree in busi-ness administration. She received her doctorate of naturopathic medicine from National College of Natural Medi-

cine, Portland, Oregon, and is a member of the Maine Association of Naturopathic Physicians and the American Association of Naturopathic Physicians. Visit her website, www.mainenaturopath.net, for more information.

TINA KACZOR, ND, FABNO, is editor in chief of Natural Medicine Journal and a natu-ropathic physician, board certified in naturo-pathic oncology. She received her naturopathic doctorate from National College of Natural Medicine, Portland, Oregon, and completed her residency in naturopathic oncology at Cancer Treatment Centers of America, Tulsa, Oklahoma. Kaczor earned undergraduate

degrees from the State University of New York at Buffalo. She is the past president and treasurer of the Oncology Association of Naturopathic Physicians and secretary of the American Board of Naturopathic Oncology. She has been published in several peer-reviewed journals. Kaczor is based in Eugene, Oregon.

JACOB SCHOR, ND, FABNO, is a grad-uate of National College of Naturopathic Medi-cine, Portland, Oregon, and now practices in Denver, Colorado. He served as president of the Colorado Association of Naturopathic Physicians and is now on the board of direc-tors of both the Oncology Association of Naturopathic Physicians and the American Association of Naturopathic Physicians. He is

recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the Interna-tional Journal of Naturopathic Medicine, Naturopathic Doctor News and Review (NDNR), and Integrative Medicine: A Clini-cian’s Journal. In 2008, he was awarded the Vis Award by the American Association of Naturopathic Physicians. His writing appears regularly in NDNR, the Townsend Letter, and Natural Medicine Journal.

JESSICA TRAN, ND, is a doctor of naturo-pathic medicine with special emphasis on the impact of environmental factors on the human body. Tran provides science-based natural medicine for the prevention and treatment of common and chronic illnesses for Well-ness Integrative Naturopathic Consulting, Inc, Irvine, California, and in her practice in Scotts-dale, Arizona.

Contributors

Tina Kaczor, ND, FABNO

Walter J. Crinnion, ND

Anne Marie Fine, NMD

Julianne Forbes, ND

Jacob Schor, ND, FABNO

Jessica Tran, ND

http://www.mainenaturopath.net

NMJ, SEPTEMBER 2015 SUPPLEMENT—VOL. 7, NO. 91 (SUPPL) ©2015 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. 5

MESSAGE FROM THE PUBLISHER

Addressing Environmental Toxicity is More Important Than Ever

The Environmental Protection Agency reports that each year, 700 new chemicals are added to the existing 84,000+ chemicals already in our lives. Of those, about 3,000 are produced or imported in volumes greater than one million pounds per year. In 2011, Vogel and Roberts reported in the journal Health Affairs that most of these chemicals enter the marketplace without comprehensive research into their toxic effects and that we need to overhaul and strengthen oversight of chemicals beyond the outdated Toxic Substances Control Act of 1976.

There is no question that we live in a toxic environment and patients—especially those who are most vulnerable and susceptible—are paying a significant price when it comes to their health. And yet treating environmentally related toxicity is something that very few conventional medical physicians understand or embrace. This treatment gap is being expertly filled by integrative practitioners who have done advanced training in the area of environmental medicine.

Diagnosing and treating environmentally related illnesses can be complex, but integrative health practitioners are uniquely poised to address and prevent them. We hope you find this issue interesting and that the information helps you address this important topic in your patients.

A special thanks to this issue’s guest editor, our very own Jacob Schor, ND, FABNO, for all of his hard work on this edition of the Natural Medicine Journal.

In good health,

Karolyn A. Gazella

Copyright © 2014 by the Natural Medicine Journal. All rights reserved.

EDITOR IN CHIEFTina Kaczor, ND, FABNO

ASSOCIATE MEDICAL EDITORJacob Schor, ND, FABNO

PUBLISHERKarolyn A. Gazella

VP, CONTENT & COMMUNICATIONSDeirdre Shevlin Bell

ASSOCIATE EDITORAnne Lanctôt

DESIGNKaren Sperry

PUBLISHED BYIMPACT Health Media, Inc.Boulder, Colorado

Natural Medicine Journal (ISSN 2157-6769) is published 14 times per year by IMPACT Health Media, Inc.. Copyright © 2015 by IMPACT Health Media, Inc.. All rights reserved. No part of this publication may be reproduced in whole or in part without written permission from the publisher. The statements and opinions in the articles in this publication are the responsibility of the authors; IMPACT Health Media, Inc. assumes no liability for any infor-mation published herein. Adver-tisements in this publication do not indicate endorsement or approval of the products or services by the editors or authors of this publica-tion. IMPACT Health Media, Inc. is not liable for any injury or harm to persons or property resulting from statements made or products or services referred to in the articles or advertisements.



Air Pollution, Disease, and MortalityParticulate matter as a global health threat

ABSTRACTThe World Health Organization has stated that air pollu-tion accounts for 1.3 million deaths worldwide every year. This article reviews the association of air pollut-ants with all major causes of death. With those asso-ciations understood, it becomes clear that outdoor air pollution is likely to be an even greater cause of mortality across the globe than is currently recognized.INTRODUCTIONThe World Health Organization (WHO) has stated that air pollution accounts for 1.3 million deaths worldwide every year.1 Upon a review of the WHO listing of the leading causes of death (Table 1), one will see that deaths from outdoor air pollutants come in just between tuberculosis and diabetes mellitus.2 This article will review the association of air pollut-ants with all the major causes of death listed below except diarrheal diseases, HIV/AIDS, tuberculosis, and traffic acci-dents. Once those associations are understood, outdoor air pollution appears likely to be an even greater cause of mortality across the globe than is currently recognized.

AIR POLLUTANTSOutdoor air is contaminated with a host of vapors, gases, and particulates from combustion (vehicular, industrial, stationary, and natural sources), evaporation, industry, agriculture, and other daily activities during which these substances become airborne. Indoor air has all the same pollutants, to which are added additional toxicants from building materials, furnish-ings, cooking, cleaning chemicals, and air fresheners, to name a few, making indoor air pollution potentially worse than outdoor.

Deaths in Millions

% of Deaths

Ischemic heart disease 7.25 12.8

Stroke 6.15 6.4

Lower respiratory infection 3.46 6.1

Chronic obstructive pulmonary disease 3.28 5.8

Diarrheal diseases 2.46 4.3

HIV/AIDS 1.78 3.1

Respiratory-tract cancers 1.39 2.4

Tuberculosis 1.34 2.4

Diabetes mellitus 1.26 2.2

Traffic accidents 1.21 2.1 Table 1. Major Causes of Death Compiled From World Health Organization Statistics1

URBAN AIR POLLUTION LEVELSThe major population centers have the greatest amount of air pollutants, mostly due to stationary energy sources and industry, as well as the huge amount of fuel burned to provide transportation. Because of the multiple health problems posed by such pollution, the United States Congress passed the Clean Air Act in 1970, which allowed the federal government to set limits for emissions from stationary and mobile sources of pollution. In May 1971, the Environmental Protection Agency (EPA) was established to implement the mandates of the Clean Air Act. Since 1970, the Clean Air Act has been amended twice (in 1977 and in 1990).3 Part of the original 1970 mandate allowed the newly formed EPA to set national ambient air quality standards for various pollutants. The EPA chose the 6 most common and most damaging pollut-ants, which are also referred to as “criteria pollutants.” These are particle pollution (often referred to as particulate matter [PM]), ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. Of the 6 pollutants, particle pollu-tion and ground-level ozone pose the most widespread health threats. These 6 are called criteria air pollutants because their permissible levels are derived from either human health-based and/or environmentally based criteria (science-based guide-lines). These criteria are referred to as “primary” when they

By Walter Crinnion, ND



are based on human health outcomes and “secondary” when they are associated with environmental or property damage.4

While all of these 6 criteria pollutants deserve attention, this article will focus on PM, the aromatic hydrocarbons it carries, and the illnesses associated with it.

PARTICULATE MATTER PM is a combination of liquid droplets (aerosols) and solid particles like dust, soot, smoke, and dirt. Particulates are found in smoke, diesel exhaust, and haze that either come directly from combustion or are products of a reaction between gases and sunlight or air. From a health perspective, PM is differen-tiated according to particle size.5 The largest of the PM, called coarse particles, are between 10 mm and 2.5 mm and are given the designation of PM10. These are often encountered near dusty roadways and industry. They are known to lodge in the trachea or bronchi. Fine particles are those between 2.5 mm and 0.1 mm in diameter and are designated as PM2.5. Fine particles can lodge in the alveoli of the lungs. Ultrafine particles (UFPs), also called nanoparticles, are less than 0.1 mm (100 nm) in size (PM<0.1). Concentrations of atmo-spheric UFPs are tens of thousands of times higher in urban air than in rural air and are considered the most detrimental of all PM fractions.6

UFPs can be either exhaled or absorbed systemically. Absorp-tion of UFPs can pose serious health risks. For example, traffic exhaust UFPs are associated with adverse effects in the respiratory, cardiovascular, and nervous systems, in addition to stimulating oxidative damage and inflammation.7 The 2 major sources of UFPs are cigarette smoke and diesel exhaust; biodiesel puts out even higher UFP levels than regular diesel.8

A recent study in Australia sought to find out where children encountered their highest exposures to UFPs. The researchers were initially quite concerned about diesel-powered school buses that often idle outside the school at the end of the school day.6 They discovered that the greatest exposure to UFPs was actually encountered at home (55% of the total daily exposure), with school exposure being the second highest source (35% of the total). Interestingly, it was not the idling buses that provided

the greatest exposure to UFPs but rather the urban background levels. The activities that were associated with the greatest expo-sure to UFPs were outdoor activities (exposure to ambient urban air), cooking and eating in the home, and commuting.

UFPs are small enough to enter the bloodstream and settle in more distant organs than the lungs. For example, UFP levels in the livers of rats 18 to 24 hours after UFP expo-sure were found to be 5 times higher than the PM levels in their lungs.9 These UFPs can also travel from the nose into the brain via the olfactory nerve.10 UFPs of iron oxide, India ink, and titanium dioxide that were initially identified in alveolar macrophages were found a day later in the lung (in the highest concentration), liver, kidney, heart, tracheobron-chial and mediastinal lymph nodes, anterior and posterior nasal cavity, the brain, and the blood. At 4 days postexpo-sure, particles were found in all of the above except for the nasal cavity and brain. At 7 days postexposure, they were still found in the lungs, liver, and blood.11 A group of rats that were exposed only once to UFPs and then sacrificed after either 3 weeks, 2 months, or 6 months showed that the UFP concentrations in the brain, heart, spleen, liver, and lungs from the single exposure slowly reduced over time, with the lungs retaining the most UFP.12 Of course, urban-dwelling humans are exposed daily and are not allowed time to clear the UFP from their organs.

UFPs cause significant oxidative damage in the tissues and organs to which they are distributed.13-15 PM in general has been associated with increased mortality primarily from cardiovascular,16,17 respiratory,18 and neoplastic diseases.19 PM of all sizes act as carriers for a number of other potent air pollutant chemicals, including polycyclic aromatic hydrocar-bons (PAHs) and volatile organic compounds (VOCs), which may account for some of their toxic health effects.20

POLYCYCLIC AROMATIC HYDROCARBONS PAHs are highly lipophilic (fat soluble) and therefore are found naturally in oil, coal, and tar deposits. They are also found in the consumer products coal tars, crude oils, creo-sote, and roofing tar. More than 100 PAHs are formed during the incomplete burning of coal, oil, and gas for fuels; the



incinerationofgarbage;smokingtobacco;orthecharbroilingof meat. In short, the burning of anything that is carbon-basedmayproducePAHs.

Table2liststhe17mostcommonPAHsaswellastheircarci-nogenic rating by the EPA and whether each is present indieselexhaust.TheEPAhasdeterminedthatbenz[a]anthra-cene,benzo[a]pyrene,benzo[b]fluoranthene,benzo[k]fluoran-thene,chrysene,dibenz[a,h]anthracene,andindeno[1,2,3-c,d]pyreneareprobablehumancarcinogens.21Benzo[a]pyreneisaknownhuman carcinogen and is themain lung carcinogenin cigarette smoke22 and vehicular exhaust.23 Both PM andPAHsareknowntodamagemitochondriaandsuppresstheirproperfunctioning.24,25

Polycyclic Aromatic Hydrocarbons

Probable Carcinogens per

US Environmental Protection Agency

Present in Diesel Exhaust

Acenapthene

Acenapthylene X

Anthracene X

Benz[a]anthracene X X

Benzo[a]pyrene X X

Benzo[e]pyrene X

Benzo[b]flouranthene X X

Benzo[j]flouranthene X

Benzo[k]flouranthene X X

Benzo[g,h,i]perylene X

Chrysene X X

Dibenzo[a,h]anthracene

X

Flouranthene X

Flourene X

Indeno[1,2,3-cd]pyrene

X X

Phenanthrene X

Pyrene X Table 2. The 17 Most Common Polycyclic Aromatic Hydrocarbons in Outdoor Air

The table shows that diesel exhaust is a major source ofthe most common PAHs, including those that are known(benzo[a]pyrene) or probable carcinogens. Benzo[a]pyreneis metabolized by cytochrome P450 1A2 and transformedinto a far more toxic metabolite: benzo[a]pyrene epoxide,highlycarcinogenic.26

INDUSTRIAL- AND VEHICLE-GENERATED VOLATILE ORGANIC COMPOUNDS VolatileOrganicCompounds (VOCs), also referred to assolvents,aretypicallyshort-chainhydrocarbonsthatevap-orate rapidly at ambient temperatures and have a varietyof industrialuses.27VOCsareused inpaints, glues, inks,fragrances, and building materials and are found in ciga-rette smoke, gasoline, and vehicular exhaust.The4mostcommon VOCs are benzene, toluene, ethylbenzene, andxylene;theyareoftenreferredtosimplyasBTEXandcanaccountforupto27%ofeachgallonofgasdispensedatthe pump for every vehicle.28 For the United States as awhole,vehicularemissionsarethegreatestsourceofthesecompoundsfoundinurbanandruralair,butinareasofthecountry where refineries and chemical plants are located,thesenonmobile sources far surpass emissionsputoutbytransportvehicles.TheEPAwebsiteprovides informationonthetotalVOCemissionsfortheentireUnitedStatesorbystateorcounty.

Datafromthe1990USEPACumulativeExposureProjectlookedat148toxicaircontaminantsforeachofthe30,803census tracts in the contiguousUnitedStates.29Concentra-tions of benzene, formaldehyde, and 1,3-butadiene weregreaterthanlevelsknowntocausecancer(cancerbenchmarklevels)inover90%ofthecensustracts.Approximately10%ofthecensustractshad1ormorecarcinogenichazardousairpollutantinconcentrationsabove1-in-10,000risklevels.Asanexample,thesedatarevealedthatof25sitesinMinnesota,10pollutantswere found that exceeded thebenchmarks in1 or more sites (acrolein; arsenic; benzene; 1,3-butadiene;carbontetrachloride;chromium;chloroform;ethylenedibro-mide;formaldehyde;andnickel).30

(continued on page 10)

http://www.epa.gov/cgi-bin/broker?_service=data&_debug=0&_program=dataprog.national_1.sas&polchoice=VOC


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The Brookhaven Medical Unit in Atlanta, Georgia, an envi-ronmentally controlled clinic, has filters of activated charcoal and aluminum oxide impregnated with potassium permanga-nate to rapidly eliminate fumes and provide less-polluted air for those in the clinic. Yet even in such a tightly controlled unit, at times of peak traffic flow, levels of hydrocarbons, and other exhaust components (carbon monoxide, chlorine dioxide, hydrogen cyanide, nitrogen dioxide, and ozone) were detected in the unit.31

A study of cyclists in an urban area showed elevated serum benzene and toluene and elevated toluene and xylenes in the urine after a 2-hour ride. Those riding in urban areas had consistently higher post-ride levels of these compounds than those riding in rural areas (details summarized in Table 3).32

Health problems associated with vehicular exhaust include increased mortality, cardiovascular illness, respiratory illness, neurological problems, and endocrine disorders including obesity, diabetes, and infertility.

MORTALITYPM, with its attached load of PAH and VOCs, has long been associated with a number of adverse health outcomes, including increased mortality. In studies done in major cities

across the globe, within 2 days of increased PM levels, the mortality rates increase.33,34 Recent estimates show that aggres-sive reductions in global PM production could reduce global annual mortality rates attributed to PM2.5 by 23%.35

CARDIOVASCULAR DISEASEMany of the deaths associated with higher levels of PM are directly due to acute myocardial infarctions (MI), to which PM is strongly linked. An article in the New England Journal of Medicine in 2004 reported that an association was found between exposure to traffic and the onset of a MI within 1 hour of beginning their morning commute (odds ratio: 2.92).36 The authors attribute at least some of this increase to vehicular exhaust exposure. Six years later, Circulation, the official journal of the American Heart Association, published a statement saying that there is an established causal relation-ship between exposure to PM2.5 and cardiovascular morbidity and mortality.37 This group also noted that reductions in PM exposure were associated with reduced rates of cardiovascular mortality within just a few years’ timeframe:

Exposure to PM<2.5µm (PM2.5) over a few hours to weeks can trigger cardiovascular disease-related mortality and nonfatal events; longer-term exposure increases the risk for cardiovascular mortality to an even greater extent than expo-sures over a few days and reduces life expectancy within the more highly exposed segments of the population by several months to a few years.37

Yet even with this clear statement by the American Heart Association, the use of measures to reduce PM exposure to prevent the number 1 killer of Americans today has received little or no public exposure.

Carotid intima-media thickness (CIMT) is used as an easily assessed surrogate marker for atherosclerosis and is a strong predictor of future cardiovascular events.38 Each standard deviation increase in CIMT is associated with a 32% increased risk of stroke and a 26% increased risk of MI. In a large study of almost 6,000 adults from 6 different US communities, it was noted that people living with higher home air PM2.5 (from both outdoor and indoor sources) had far greater CIMT

Rural Rides (blood ng/L)

Urban Rides (blood ng/L)

Pre-ride Post-ride Pre-ride Post-rideBenzene 190.0 188.9 186.1 224.2Toluene 310.1 320.2 310.3 436.3Ethylbenzene 232.0 237.0 239.0 292.5Xylenes 735.0 697.3 831.4 1190.0

Rural Rides (urine ng/L)

Urban rides (urine ng/L)

Pre-ride Post-ride Pre-ride Post-rideBenzene 127.6 112.4 104.2 120.5Toluene 282.0 280.1 295.1 338.3Ethylbenzene 82.8 86.1 70.1 74.5Xylenes 210.4 219.0 220.3 251.1

Table 3. Data From Bergamaschi et al: “Bicyclist Biomarkers of Internal Dose in Pre-ride and Post-ride Blood and Urine Samples”32



progression than those with lower PM2.5 exposure.39 These data corroborated a prior study of adults living in the Los Angeles, California, basin that showed air pollution is associ-ated with progression of atherosclerosis via CIMT testing.40

CIMT has been directly linked with PAH levels as well. A study of Brazilian cab drivers and non‒cab driving controls measured 1-hydroxypyrene (1-OHP), a common metabolite of traffic-related PAH compounds and a validated marker for PAH exposure, along with other indices of cardiovascular inflammation and disease.41 The taxi drivers had significantly higher levels of 1-OHP along with higher levels of oxidized low-density lipoprotein (LDL), homocysteine, high- sensitivity c-reactive protein, and other proinflammatory cytokine markers. The researchers also reported that the taxi drivers had significantly lower levels of glutathione peroxidase and glutathione transferase function, as well as lower levels of ascorbic acid. This group of researchers then took the study 1 step further and looked at the level of atherosclerosis that was present in the drivers and controls to see how that related to all of these other markers.42 This was the study in which 1-OHP was directly linked with not only serum homocysteine levels, but also greater CIMT. Interestingly, the CIMT was not asso-ciated with total cholesterol, triglycerides, or LDL levels.

Hypertension is a major risk factor for both stroke and heart attack, as well as increased morbidity to other organs in the body; it is also clearly associated with air pollution levels.43 Long-term exposure to elevated levels of all PM sizes leads to an elevation in diastolic blood pressure in both adults and children.44,45 Inter-estingly, this effect is heightened in people who are obese46 and who are psychologically stressed,47 while the effect is reduced in those children who were breastfed.48 Not only can vehicular exhaust particulate matter levels increase diastolic blood pres-sure, but biological PM49 (commonly found in indoor air) and the use of biomass fuel can do the same.50

RESPIRATORY ILLNESSIt has long been established that children have far higher rates of asthma, bronchitis, bronchiolitis, pneumonia, phlegm production, and wheezing when exposed to vehicular exhaust.51 Several studies have looked at the rates of respira-

tory disease in those living close to busy roadways vs those who live farther from main thoroughfares. All such studies have confirmed that the closer one is to a higher level of vehic-ular exhaust (especially diesel truck exhaust), the greater the risk of asthma.52,53 One of the largest studies to date to explore the association between air pollution and respiratory disease is the European Study of Cohorts for Air Pollution Effects project, which encompasses 10 European birth cohorts in 6 countries with a total of 16,059 children.54 The authors found that exposure to air pollution clearly increased the risk of pneumonia in the children they followed.

While respiratory and cardiovascular effects of air pollution have long been associated with mortality, recent studies are linking it to a number of other issues, including neurological and endocrine issues.

NEUROLOGICAL EFFECTSExposure to vehicular exhaust has been clearly linked to reduced cognitive functioning in both children and adults. In adults, it has been associated with depression, and in children, it may influence the risk and severity of autistic spectrum disorder. Prenatal exposure to PAH compounds from vehic-ular exhaust leads to reduced intelligence quotient (IQ) levels in children. An ongoing study in New York City has been following a birth cohort of 249 children whose mothers were assessed for PAH exposure with personal air monitors during their third trimester. By the age of 3, the children whose mothers had median or higher levels of PAH exposure showed developmental delay.55 By the age of 5, these same children showed full scale IQ and verbal IQ levels that were signifi-cantly lower than children with lower prenatal PAH exposure (P=0.009).56 A similarly designed study in Krakow, Poland, also measured mothers’ PAH exposure and found similar IQ point loss in the 5-year-old children who had greater prenatal PAH exposure.57 The researchers who followed the cohort in New York later published their estimate of the economic effects on these 249 children based on their lifetime earning if a modest reduction in PAH could be achieved. Their published finding proposed that a mere 0.25 ng/m3 reduction of PAHs, achievable by good indoor air purification, would boost the lifetime earnings of the cohort by $215 million.58



A number of convincing studies have also been published revealing the association between vehicular exhaust and both rates and severity of autism. Children who were gestationally exposed to high levels of vehicular exhaust were twice as likely to be autistic as those who had lower exposures, while those with higher exposure during the first year of life had triple the risk.59 The closer the mothers-to-be lived to a freeway, the higher the risk for having an autistic child.60 Subsequent studies have found that exposure to vehicular exhaust during the first and second trimesters do not increase the risk, but exposure during the third trimester does.61,62 Diesel exhaust turned out to be the greatest exhaust-source risk for the development of autism in the Children of Nurses’ Health Study II.63

The effect of PM on cognition in adults was the focus of a study that involved the 19,409 women in the Nurses’ Health Study Cognitive Cohort. These women ranged in age from 70 to 81 years, and their cognitive measurements were corre-lated with PM (both PM10 and PM2.5) levels.64 They found that women who were exposed to higher levels of both PM10 and PM2.5 for 7 to 14 years had significantly faster cogni-tive decline as they aged. The researchers were actually able to quantify the cognitive decline in relation to the levels of PM, showing that an increase of 10 µg/m3 of long-term PM 2.5 exposure resulted in the same reduction in cognition as would occur from 2 years of aging in those between the ages of 70 and 81 years. A similar result was reported by a group of researchers who used data from the US Department of Veterans Affairs Normative Aging Study.65 This group of males with an average age of 71 years had been administered cogni-tive testing 7 times during an 11-year period while levels of black carbon were used as a marker for vehicular exhaust. The researchers reported that for every doubling of the ambient levels of black carbon, the participants experienced a cognitive decline that was equivalent to 1.9 years of aging. In addition to cognitive decline, 2 studies have now clearly linked urban air pollution to increased risk of depression.66,67

ENDOCRINE EFFECTSUrban air pollution has been linked to increased risk of infer-tility, obesity, and diabetes, all common problems in the modern

population. Italian traffic policemen who were exposed daily to vehicular exhaust throughout their shifts had significantly lower levels of free testosterone than police assigned to other duties.68 Exposure to vehicular exhaust and cigarette smoke are also strongly associated with multiple sperm abnormali-ties associated with male infertility.69-71 Similarly, exposure to vehicular exhaust is also associated with increased female infer-tility rates.72 In infertile couples who have chosen to undergo in vitro fertilization, PM exposure during the preconception period also greatly increases risk of pregnancy loss.73

Children exposed to higher levels of vehicular air pollutants were up to 3 times more likely to develop type 1 diabetes than children breathing air with lower levels of vehicular exhaust compounds.74 In this study, the highest diabetes risk came from exposure to high levels of ozone derived from traffic sources. In a group of almost 400 German 10-year-olds, exposure to vehicular exhaust increased their incidence of insulin resistance, one of the first steps to developing type 2 diabetes.75 Long-term exposure to vehicular PM has also been directly associated with higher risk in adults for developing both metabolic syndrome and type 2 diabetes.76,77 Exposure to high levels of PM2.5 during the second trimester of pregnancy gave women a far higher risk of developing impaired glucose tolerance during pregnancy.78 Women with the highest PM2.5 exposure levels and with the closest proximity of heavy traffic were 2.6 times more likely to have problems with their blood sugar levels, although no direct link was found between vehic-ular exhaust and the risk of overt gestational diabetes mellitus.

As mentioned previously, PM from vehicular exhaust is known to lead to increased risk of the development of meta-bolic syndrome, one of whose manifestations is increased body weight. PAHs from urban air and from environ-mental tobacco smoke (ETS) are both associated with hugely increased risk levels for childhood obesity. Using data from the 2003-2008 National Health and Nutrition Examina-tion Survey, researchers found that children in the second, third, and fourth quintiles of urinary PAH metabolites had risk factors for obesity that were 4.51, 2.57, and 8.09 times greater, respectively, than those in the lowest quintile.79 For



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the children exposed to both the higher PAH levels and ETS, the levels went up even higher, showing a clear synergistic effect leading to far greater body mass index in these children.

CONCLUSIONAir is vital for human life, with the average adult inhaling more than 17,000 times every day. Unfortunately, with very few exceptions, each of those daily breaths may come with a substantial number of toxicants with severe health conse-quences. In fact, adverse health effects of air pollutants include cardiovascular disease, which is the most common cause of death in North America. These same air pollutants are associated with a variety of adverse respiratory, neuro-logical, hormonal, and cognitive effects; they also increase a woman’s risk of having an autistic child. Much more focus needs to be placed on recognizing the important role that common air pollutants hold in health, with commensurate actions being taken to reduce the levels of common air pollut-ants in the home—the one environment most people are in control of. It is quite possible that one of the most effective preventive medicine modalities would be the installation of a high-quality air purifier in the home.

REFERENCES1 World Health Organization. The top 10 causes of death. Available at: http://www.who.

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6 Mazaheri M, Clifford S, Jayaratne R, et al. School children’s personal exposure to ultra-fine particles in the urban environment. Environ Sci Technol. 2014;48(1):113-120.

7 Kumar S, Verma MK, Srivastava AK. Ultrafine particles in urban ambient air and their health perspectives. Rev Environ Health.2013;28(2-3):117-128.

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9 Oberdorster G, Sharp Z, Atudorel V, et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A. 2002;65(20):1531-1543.

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27 US Geological Survey. Volatile organic compounds (VOCs). Available at: http://toxics.usgs.gov/definitions/vocs.html. Accessed August 31, 2015.

28 Bolden AL, Kwiatkowski CF, Colborn T. New look at BTEX: Are ambient levels a problem? Environ Sci Technol. 2015;49(9):5261-5276. Epub 2015 Apr 15.

29 Woodruff TJ, Axelrad DA, Caldwell J, Morello-Frosch R, Rosenbaum A. Public health implications of the 1990 toxics concentrations across the United States. Environ Health Perspect. 1998;106(5):245-251.

30 Pratt GC, Palmer K, Wu CY, Oliaei F, Hollerbach C, Fenske MJ. An assessment of air toxics in Minnesota. Environ Health Perspect.2000;108(9):815-825.

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32 Bergamaschi E, Burstolin A, De Palma G, et al. Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons. Toxicol Lett. 1999;108(2-3):241-247.

33 Peters A, Skorkovsky J, Kotesovec F, et al. Associations between mortality and air pollu-tion in central Europe. Environ Health Perspect.2000;108(4):283-287.

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35 Apte JS, Marshall JD, Cohen AJ, Brauer M. Addressing global mortality from ambient PM2.5. Environ Sci Technol. 2015;49(13):8057-8066. Epub 2015 Jun 16.

36 Peters A, von Klot S, Heier M, et al; Cooperative Health Research in the Region of Augs-burg Study Group. Exposure to traffic and the onset of myocardial infarction. N Engl J Med. 2004;351(17):1721-1730.

37 Brook RD, Rajagopalan S, Pope CA 3rd, et al; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378.



38 Lorenz M, Markus H, Bots M, Rosvall M, Sitzer M. Prediction of clinical cardiovas-cular events with carotid intima-media thickness. A systematic review and meta-anal-ysis. Circulation. 2007;115(4):459-467.

39 Adar SD, Sheppard L, Vedal S, et al. Fine particulate air pollution and the progression of carotid intima-medial thickness: a prospective cohort study from the multi-ethnic study of atherosclerosis and air pollution. PLoS Med. 2013;10(4):e1001430.

40 Künzli N, Jerrett M, Garcia-Esteban R, et al. Ambient air pollution and the progression of atherosclerosis in adults. PLoS One.2010;5(2):e9096.

41 Brucker N, Moro AM, Charão MF, et al. Biomarkers of occupational exposure to air pollu-tion, inflammation and oxidative damage in taxi drivers. Sci Total Environ. 2013;463-464:884-893.

42 Brucker N, Charão MF, Moro AM, et al. Atherosclerotic process in taxi drivers occupa-tionally exposed to air pollution and co-morbidities. Environ Res. 2014 May;131:31-38.

43 Wong MC, Tam WW, Wang HH, et al. Exposure to air pollutants and mortality in hyper-tensive patients according to demography: a 10 year case-crossover study. Environ Pollut. 2014 Sep;192:179-185.

44 Chen SY, Wu CF, Lee JH, et al. Associations between long-term air pollutant exposures and blood pressure in elderly residents of Taipei City: a cross-sectional study. Environ Health Perspect. 2015;123(8):779-784. Epub 2015 Mar 20.

45 Dong GH, Wang J, Zeng XW, et al. Interactions between air pollution and obesity on blood pressure and hypertension in Chinese children. Epidemiology. 2015;26(5):740-747.

46 Qin XD, Qian Z, Vaughn MG, et al. Gender-specific differences of interaction between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study. Sci Total Environ. 2015 Oct 1;529:243-248.

47 Hicken MT, Dvonch JT, Schulz AJ, Mentz G, Max P. Fine particulate matter air pollu-tion and blood pressure: the modifying role of psychosocial stress. Environ Res. 2014 Aug;133:195-203.

48 Dong GH, Qian ZM, Trevathan E, et al. Air pollution associated hypertension and increased blood pressure may be reduced by breastfeeding in Chinese children: the Seven Northeastern Cities Chinese Children’s Study. Int J Cardiol. 2014;176(3):956-961.

49 Zhong J, Urch B, Speck M, et al. Endotoxin and ?-1,3-d-glucan in concentrated ambient particles induce rapid increase in blood pressure in controlled human expo-sures. Hypertension. 2015;66(3):509-516. Epub 2015 Jun 29.

50 Burroughs Peña M, Romero KM, Velazquez EJ, et al. Relationship between daily exposure to biomass fuel smoke and blood pressure in high-altitude Peru. Hyperten-sion. 2015;65(5):1134-1140.

51 Ciccone G, Forastiere F, Agabiti N, et al. Road traffic and adverse respiratory effects in children. SIDRIA Collaborative Group. Occup Environ Med. 1998;55(11):771-778.

52 Cook AG, deVos AJ, Pereira G, Jardine A, Weinstein P. Use of a total traffic count metric to investigate the impact of roadways on asthma severity: a case-control study. Environ Health. 2011 Jun 2;10:52.

53 Li S, Batterman S, Wasilevich E, Elasaad H, Wahl R, Mukherjee B. Asthma exacerba-tion and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan. Environ Health. 2011 Apr 23;10:34.

54 Macintyre EA, Gehring U, Mölter A, et al. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project. Environ Health Perspect. 2013;122(1):107-113.

55 Perera F, Rauh V, Whyatt RM, et al. Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environ Health Perspect. 2006;114(8):1287-1292.

56 Perera FP, Li Z, Whyatt R, et al. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics.2009;124(2):e195-202.

57 Edwards SC, Jedrychowski W, Butscher M, et al. Prenatal exposure to airborne poly-cyclic aromatic hydrocarbons and children’s intelligence at 5 years of age in a prospec-tive cohort study in Poland. Environ Health Perspect. 2010;118(9):1326-1331.

58 Perera F, Weiland K, Neidell M, Wang S. Prenatal exposure to airborne polycyclic aromatic hydrocarbons and IQ: Estimated benefit of pollution reduction. J Public Health Policy. 2014;35(3):327-336.

59 Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-related air pollu-tion, particulate matter, and autism. JAMA Psychiatry. 2013;70(1):71-77.

60 Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study.Environ Health Perspect. 2011;119(6):873-877.

61 Kalkbrenner AE, Windham GC, Serre ML, et al. Particulate matter exposure, prenatal and postnatal windows of susceptibility, and autism spectrum disorders. Epidemi-ology. 2015;26(1):30-42.

62 Raz R, Roberts AL, Lyall K, et al. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case-control analysis within the Nurses’ Health Study II Cohort. Environ Health Perspect. 2015;123(3):264-270.

63 Roberts AL, Lyall K, Hart JE, et al. Perinatal air pollutant exposures and autism spec-trum disorder in the children of Nurses’ Health Study II participants. Environ Health Perspect. 2013;121(8):978-984.

64 Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F. Exposure to particu-late air pollution and cognitive decline in older women. Arch Intern Med. 2012;172(3):219-227.

65 Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Spiro A 3rd, Schwartz J. Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect. 2011;119(5):682-687.

66 Cho J, Choi YJ, Suh M, et al. Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma. J Affect Disord. 2014 Mar;157:45-51.

67 Lim YH, Kim H, Kim JH, Bae S, Park HY, Hong YC. Air pollution and symptoms of depression in elderly adults. Environ Health Perspect.2012;120(7):1023-1028.

68 Sancini A, Tomei F, Tomei G, et al. Exposure to urban stressors and free testosterone plasma values. Int Arch Occup Environ Health. 2011;84(6):609-616.

69 Rengaraj D, Kwon WS, Pang MG. Effects of motor vehicle exhaust on male reproduc-tive function and associated proteins. J Proteome Res. 2015;14(1):22-37.

70 Richthoff J, Elzanaty S, Rylander L, Hagmar L, Giwercman A. Association between tobacco exposure and reproductive parameters in adolescent males. Int J Androl. 2008;31(1):31-39.

71 Rubes J, Selevan SG, Evenson DP, et al. Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality. Hum Reprod. 2005;20(10):2776-2783.

72 Nieuwenhuijsen MJ, Basagaña X, Dadvand P, et al. Air pollution and human fertility rates. Environ Int. 2014 Sep;70:9-14.

73 Perin PM, Maluf M, Czeresnia CE, Januário DA, Saldiva PH. Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET). J Assist Reprod Genet. 2010;27(7):371-382.

74 Hathout EH, Beeson WL, Ischander M, Rao R, Mace JW. Air pollution and type 1 diabetes in children. Pediatr Diabetes. 2006;7(2):81-87.

75 Thiering E, Cyrys J, Kratzsch J, et al. Long-term exposure to traffic-related air pollu-tion and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts. Diabetologia. 2013;56(8):1696-1704.

76 Eze IC, Schaffner E, Foraster M, et al. Long-term exposure to ambient air pollution and metabolic syndrome in adults. PLoS One.2015;10(6):e0130337.

77 Weinmayr G, Hennig F, Fuks K, et al; Heinz Nixdorf Recall Investigator Group. Long-term exposure to fine particulate matter and incidence of type 2 diabetes mellitus in a cohort study: effects of total and traffic-specific air pollution. Environ Health. 2015 Jun 19;141:53.

78 Fleisch A, Gould D, Rifas-Shiman S, et al. Air pollution exposure and abnormal glucose tolerance during pregnancy: the project viva cohort. Environ Health Perspect. 2014;122(4):378-383.

79 Kim HW, Kam S, Lee DH. Synergistic interaction between polycyclic aromatic hydrocar-bons and environmental tobacco smoke on the risk of obesity in children and adoles-cents: The U.S. National Health and Nutrition Examination Survey 2003-2008. Environ Res. 2014 Nov;135:354-360.


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REFERENCE Power MC, Kioumourtzoglou MA, Hart JE, Okereke OI, Laden F, Weisskopf MG. The relation between past expo-sure to fine particulate air pollution and prevalent anxiety: observational cohort study. BMJ. 2015 Mar 24;350:h1111.

DESIGNThis observational cohort study’s purpose was to deter-mine whether higher past exposure to particulate air pollu-tion can be associated with high symptoms of anxiety.

PARTICIPANTSThe researchers selected 71,271 women enrolled in the Nurses’ Health Study (NHS) who lived in the contiguous United States and for whom valid data of particulate matter (PM) exposure were available during the time periods of interest. Ages ranged between 57 and 85 years (mean: 70 y).

MEASURESParticulate exposureUsing home addresses, which were updated every 2 years as part of the NHS, the researchers used latitude and longi-tude data to estimate particulate air pollution exposure measured via levels of PM; this pollution was character-ized by standard size categories (PM2.5 or PM10) during the 1-month, 3-month, 6-month, 1-year, and 15-year time periods prior to an assessment of the participants for anxiety symptoms. Distance of residence from major roads 2 years before anxiety assessment was also determined.

AnxietyAnxiety levels were assessed using the Crown-Crisp index’s phobic anxiety subscale.

KEY FINDINGSHigher exposure to particulates in the PM2.5 range (<2.5 μm in diameter) was significantly associated with increased odds of high anxiety symptoms over multiple time periods. As an example, every per 10 μg/m3 increase in the prior 1-month average of PM2.5 increased odds of high-level anxiety by 12% (odds ratio [OR]:1.12; 95% confidence interval [CI]:1.06-1.19). This same increase in exposure to PM2.5 over the previous 12 months increased odds of high anxiety only slightly more, by 15% [OR:1.15, CI: 1.06-1.26]. Short-term exposure appeared more relevant than long-term exposure, with more recent exposures poten-tially more relevant than more distant exposures. Neither the larger particulate size PM10 (2.5 μm-10 μm in diameter) nor proximity of residence to major roads appeared to be associated with anxiety.

ABSTRACT & COMMENTARY

Does Air Pollution Make Women Anxious?Teasing out the relationship between fine particulate exposure and mood

PRACTICE IMPLICATIONSThe potential link between particulate levels and anxiety levels is surprising. Until now, we have associated high levels of particulate matter mainly with cardiovascular disease (CVD) and respiratory illness; as Walter Crinnion, ND, notes in this issue of the Natural Medicine Journal, particulate matter is “associated with adverse effects in the respiratory, cardiovascular, and nervous systems, in addition to stimulating oxidative damage and inflammation.”

The idea that PM pollutants might impact mood is relatively new. The majority of such papers have focused on depressive symptoms. In a 2012 article on premenopausal women in rural India, Bannerjee et al reported a strong correlation between depression and cooking with biomass pellets made of reprocessed organic material. The explanation offered to explain this associa-tion was the high PM levels in the participants’ homes, the result of this cooking method.1 Likewise, in a 2014 publication, Cho reported a significant association between air pollutant levels in Korea with the number of emergency room visits for depres-sive complaints.2

In a January 2015 review, Tzivian et al reported on 15 articles that related to the long-term effects of air pollution and ambient noise levels on cognitive and psychological function in adults. Their conclusion: “Both exposures were separately shown to be associated with one or several measures of global cognitive function, verbal and nonverbal learning and memory, activi-ties of daily living, depressive symptoms, elevated anxiety, and nuisance.”3 Unfortunately no study examined both exposures at the same time, and it is often hard to separate the 2 factors.3 For example, an April 2015 study tells us that traffic wardens in Paki-stan have above-average levels of depression, stress, public conflict, irritation, behavioral problems, speech interference, hyperten-sion, loss of concentration, hearing impairment, headache, and CVD. The authors of this study blamed high noise levels for these cognitive effects, though they neglected to report PM exposure levels.4 One would suspect such exposure was high.

A March 2014 study that sought an association between particu-late matter levels and depression in Boston was unable to prove one5; this article was immediately criticized for its methodology.6

By Jacob Schor, ND, FABNO


The smallest of the airborne particles (PM0.1 or smaller) are small enough to cross from lungs to blood and then across the blood brain barrier to reach the brain. In addition, larger particulates (PM2.5 and PM10) can carry small molecules such as solvent residue, which then traverses the alveoli and enters the bloodstream directly. This is probably why air pollution is associated with stroke and depression in adults and why children exposed to pollution “show significant systemic inflammation, immunodysregulation at systemic, intrathechal and brain levels, neuroinflammation and brain oxidative stress, along with the main hallmarks of Alzheimer and Parkinson’s diseases.”7

This current report of a significant association with PM and anxiety should not come as a surprise. The only surprise is that we hadn’t considered this possibility until now. These results certainly have a clear clinical implication. We should consider the potential impact of air quality on any patient with anxiety symptoms.

Potential improvement in anxiety symptoms might be achieved if patients simply use an air filter at home. Few medical interventions will come with a lower risk profile than this, a consideration often important for anxious patients. The potential side effects of using an air filter are all desir-able, particularly reduced CVD risk and according to a March 2015 paper, reduced risk of stroke.8

REFERENCES1 Banerjee M, Siddique S, Dutta A, Mukherjee B, Ranjan Ray M. Cooking with biomass

increases the risk of depression in pre-menopausal women in India. Soc Sci Med. 2012 Aug;75(3):565-572.

2 Cho J, Choi YJ, Suh M, et al. Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma. J Affect Disord. 2014 Mar;157:45-51.

3 Tzivian L, Winkler A, Dlugaj M, et al. Effect of long-term outdoor air pollution and noise on cognitive and psychological functions in adults. Int J Hyg Environ Health. 2015;218(1):1-11.

4 Tabraiz S, Ahmad S, Shehzadi I, Asif MB. Study of physio-psychological effects on traffic wardens due to traffic noise pollution; exposure-effect relation. J Environ Health Sci Eng. 2015 Apr 16;13:30.

5 Wang Y, Eliot MN, Koutrakis P, et al. Ambient air pollution and depressive symp-toms in older adults: results from the MOBILIZE Boston study. Environ Health Perspect. 2014;122(6):553-558.

6 Gao Y, Xu T, Sun W. Ambient air pollution and depressive symptoms in older adults. Environ Health Perspect. 2015;123(5):A114.

7 Calderón-Garcidueñas L, Calderón-Garcidueñas A, Torres-Jardón R, Avila-Ramírez J, Kulesza RJ, Angiulli AD. Air pollution and your brain: what do you need to know right now. Prim Health Care Res Dev. 2015;16(4):329-345.

8 Shah AS, Lee KK, McAllister DA, et al. Short term exposure to air pollution and stroke: systematic review and meta-analysis. BMJ. 2015 Mar 24;350:h1295.


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REFERENCE Guida M, Troisi J, Ciccone C, et al. Bisphenol A and congen-ital developmental defects in humans. Mutat Res. 2015 Apr; 774:33-39. Epub 2015 Mar 6.

DESIGNCase-control study

PARTICIPANTSOne hundred fifty-one preg-nant women were divided into 2 groups: the case group (n=101) consisted of women with established diagnosis of fetal malformation and the control group (n=50) consisted of women who visited the hospital during routine evalua-tions.

STUDY INTERVENTIONTotal, free, and conjugated bisphenol A (BPA) levels were measured in participants’ blood using gas chromatog-raphy–mass spectrometry with isotropic dilution.

KEY FINDINGSThe average value of free BPA was nearly 3 times greater in the cases of chromosomal malformations and nearly 2 times greater in cases of central and peripheral nervous system nonchromosomal malforma-tions compared to controls. Conjugated BPA levels, which were higher in the control group, support the hypoth-esis that a reduced ability to metabolize the chemical in the mother can lead to the occur-rence of malformation in the fetus.

PRACTICE IMPLICATIONSVarious studies point to BPA as an endo-crine-disruptor that interferes with the programming of complex endocrine path-ways during in utero and early childhood development.1-3 This is one of the first studies conducted in humans to explore the correla-tion between maternal blood BPA and fetal malformations. The most interesting obser-vation from the study is that the control group with normally developed fetuses had higher levels of BPA conjugate compared to the case group of women with malformed fetuses. This finding reflects the ability of the control group to metabolize BPA to its inert form. The conjugated forms of BPA do not have endocrine-like activity and do not alter the biological processes of fetal develop-ment. Nonconjugated BPA binds to plasma proteins and interferes with the endocrine system, leading to fetal malformations.

A study conducted by Matsumoto et al in 2002 on BPA pharmacokinetics demonstrated that the end result of BPA metabolism is eliminated via the kidneys as a water-soluble formation of BPA-gluc-uronide occurring via hepatic glucurono-syltransferase (GT).4 Another metabolite of BPA can occur, to a lesser degree, by sulfotransferase, resulting in the forma-tion of BPA-sulfate. Hepatic GT activity is dependent on age and is much lower in fetuses and neonates.5 The major route of BPA metabolism in fetuses and neonates is via sulfation.6,7

This study clearly illustrates the environ-mental medicine concept of total body burden. The accumulation of toxicant load over time predisposes individuals to be more

susceptible to chronic illnesses and diseases. Reports of decreased fertility over the last decade may be attributed to long-term exposure to BPA, which has been linked to decreases in the percentage of oocytes that develop during meiosis II.8,9 The mecha-nism of action of BPA on oocytes remains unknown. From the study’s findings, the authors hypothesize the reduced ability to metabolize BPA may predispose a woman to pregnancies with fetal chromosomal abnor-malities. These women can be classified as “poor metabolizers” who were more suscep-tible to the endocrine disruption of BPA. The results of the study also confirm the correlation between blood concentrations of total BPA in women with fetuses that had chromosomal abnormality compared to women with normally developed fetuses, as demonstrated by Yamada et al.10

It is imperative that clinicians educate patients on sources of BPA exposure to reduce or eliminate exposure for potential harm. Expo-sure to BPA is ubiquitous: the substance is found in plastics, linings of cans for food and beverages, thermal receipts, dental seal-ants, and self-adhesive labels, among several sources.11 A significant finding of this study highlights that those with normal biotrans-formation processes or ability to detoxify do not seem to exhibit the same deleterious effects of BPA as those who do are not able to clear exogenous compounds as well. Another focus in preconception care and infertility evaluation needs to be placed on identifying how well a woman can adequately clear toxi-cant exposures.

Nutrients provided to patients prior to conception should focus on all aspects of biotransformation, especially on hepatic


Bisphenol A and Pregnant WomenStudy warns of fetal malformation in “poor metabolizers” of BPA By Jessica Tran, ND


GT activity to improve clearance of BPA to its nonactive forms and prevent harm to the developing fetus. Another note to emphasize is that BPA substitutes bisphenol S (BPS) and bisphenol-F (BPF) can also have the same endocrine-disrupting effects as BPA since they are as hormonally active.12 BPS and BPF can be found in the same sources as BPA—personal care products, paper products, and food.

This study is a wake-up call to the role of BPA exposure on fetal development and human reproduction. Further explo-ration is warranted to determine its effects, if any, on male fertility and contribution to fetal malformation.

REFERENCES1 Suk WA, Murray K, Avakian MD. Environmental hazards to children’s health in the

modern world. Mutat Res. 2003;544(2-3):235-242. 2 Wang MH, Baskin LS. Endocrine disruptors, genital development, and hypospadias. J

Androl. 2008;29(5):499-505.

3 Unüvar T, Büyükgebiz A. Fetal and neonatal endocrine disruptors. J Clin Res Pediatr Endocrinol. 2012;4(2):51-60.

4 Matsumoto J, Yokota H, Yuasa A. Developmental increases in rat hepatic microsomal UDP-glucuronosyltransferase activities toward xenoestrogens and decreases during pregnancy. Environ Health Perspect. 2002;110(2):193-196.

5 Domoradzki JY, Thornton CM, Pottenger LH, et al. Age and dose dependency of the pharmacokinetics and metabolism of bisphenol A in neonatal Sprague-Dawley rats following oral administration. Toxicol Sci. 2004;77(2):230-242.

6 Chapin RE, Adams J, Boekelheide K, et al. NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A. Birth Defects Res B Dev Reprod Toxicol. 2008;83(3):157-395.

7 Suiko M, Sakakibara Y, Liu MD. Sulfation of environmental estrogen-like chemicals by human cystolic sulfotransferases. Biochem Biophys Res Commun. 2000;267(1):80-84.

8 Guzick DS, Swan S. The decline of infertility: apparent or real? Fertil Steril. 2006;86(3):524-526; discussion 534.

9 Hamilton BE, Ventura SJ. Fertility and abortion rates in the United States, 1960-2002. Int J Androl. 2006;29(1):34-45.

10 Yamada H, Furuta I, Kato EH, et al. Maternal serum and amniotic fluid bisphenol A concentrations in the early second trimester. Reprod Toxicol. 2002;16(6):735-739.

11 Mikolajewska K, Stragierowicz J, Gromadzinsk J. Bisphenol A— Application, sources of exposure and potential risks in infants, children and pregnant women. Int J Occup Med Environ Health. 2015;28(2):209-241.

12 Rochester JR, Bolden AL. Bisphenol S and F: A systematic review and comparison of the hormonal activity of bisphenol A substitutes.Environ Health Perspect. 2015;123(7):643-650.


http://www.econugenics.com/ecodetox/

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http://www.econugenics.com


REFERENCE Quach T, Von Behren J, Goldberg D, Layefsky M, Reynolds P. Adverse birth outcomes and maternal complications in licensed cosmetologists and manicurists in California. Int Arch Occup Environ Health. 2014 Dec 14. [Epub ahead of print]

DESIGNThis was a population-based retrospective study of cosmetolo-gists and manicurists in California designed to examine adverse pregnancy outcomes as compared to both the general female population and to women working in other industries. A restricted analysis was also conducted for Vietnamese women who comprise a significant proportion of the nail and hair care work-force.

PARTICIPANTSThe California licensing agency for cosmetologists and manicur-ists database, which included a total of 260,052 licensed cosme-tologists and 159,430 licensed manicurists, was matched up to the birth registry files to identify births occurring between 1996 and 2009, a 14-year study period. The examined births were restricted to singletons and to women who were at least 18 years old at the age of birth. This resulted in 81,205 identified births among this group.

For the 2 comparison groups, births during the same timeframe by women from the general population were frequency-matched at a 5-to-1 ratio by year of birth, resulting in 406,025 live births. The second comparison group consisted of women who had occupa-tions on the birth records listed as teacher, realtor, salesperson, banker, office worker, and food service worker. This group totaled 53,056 live births.

STUDY PARAMETERS ASSESSEDOutcome measures were birthweight, gestational age, selected birth defects, and infant death, as well as maternal preeclampsia, gestational and unspecified diabetes, premature rupture of membranes, placental abruption, plancenta previa, precipitous labor, and prolonged labor.

PRIMARY OUTCOME MEASURESLow birthweight was defined as less than 2,500 g (5.51 lb), preterm delivery defined as less than 37 weeks vs 37 weeks or more, and infant death defined as death during the first year of life. Babies below the 10th percentile of weight using sex-specific percentiles were identified as small for gestational age (SGA). Maternal outcomes included preeclampsia, gestational diabetes (data was available only for births between 2006 and 2009 since previous years did not specify “gestational diabetes” for those who

were identified as having diabetes), chronic diabetes, prolonged labor, precipitous labor, premature rupture of membranes, placental abruption, and placenta previa (data available for births between 1996 and 2005 only).

KEY FINDINGSIncreased risk for adverse birth outcomes in cosmetologists and manicurists among all races was not observed. Cosmetologists had slightly reduced risk for low birthweight, SGA, and infant death compared to the general population. However, an increased risk of SGA in Vietnamese manicurists and cosmetologists was found when compared to other working women: odds ratio (OR):1.39; 95% confidence interval (CI):1.08-1.78 for manicurists and OR:1.40; 95% CI:1.08-1.83 for cosmetologists. These results were statistically significant. Some maternal complications were observed, most notably an increased risk for gestational diabetes (OR:1.28; 95% CI:1.10-1.50 for manicurists and OR:1.19; 95% CI:1.07-1.33 for cosme-tologists) compared with the general population, which was further elevated when restricted to the Vietnamese workers (OR:1.59; 95% CI:1.2-2.11 for manicurists and OR:1.49; 95% CI:1.04-2.11 for cosmetologists). These results attained statistical significance. Unspecified diabetes also posed a statistically significant elevation in risk for manicurists (OR:1.36; 95% CI:1.08-1.71) compared with the general population. A less significant increased risk was observed in cosmetologists (OR:1.14; 95% CI:1.0-1.30) compared with the general population. These increases in risk were not statistically significant in the manicurists and cosmetologists when compared with other working women, although increases in risk were noted. There was also a statistically significant increase in risk of diabetes (unspecified) in the Vietnamese women breakout group of mani-curists compared with the general population (OR:1.98; 95% CI:1.03-3.83) and also for gestational diabetes for the Vietnamese manicurists (OR:1.59; 95% CI:1.20-2.11) and cosmetologists (OR:49; 95% CI:1.04-2.11). Increased risk of premature rupture of membranes was statisti-cally significant in manicurists but not cosmetologists as compared with other working women (OR:1.15; 95% CI:1.01-1.31) and as compared with the general population (OR:1.21; 95% CI:1.09-1.35). Increased risk of placentia previa was also statistically signif-icant (OR:1.46; 95% CI:1.08-1.97 for manicurists and OR:1.22; 95% CI:1.02-1.46 for cosmetologists) when compared with the general population but was not statistically significant when compared with other working women.


Are Cosmetologists and Manicurists at Greater Risk for Pregnancy Complications?Study illuminates potential health risks for women in the nail and hair care industry

By Anne Marie Fine, NMD


www.breathtests.com



PRACTICE IMPLICATIONSAs the authors of the present study note, manicurists and cosmetologists are exposed daily to an array of potentially hazardous chemicals associated with nearly every hair and nail care service they provide. These chemicals have received considerable attention in recent years because some of them are known or suspected carcinogens and endocrine-disruptors. Previous studies have demonstrated reproduc-tive abnormalities in humans and animals exposed to these compounds. However, despite the growth of this industry and the numerous chemicals of concern found in salons, very few human health studies have been conducted in this area.

An investigation of the nail worker industry was published in the New York Times on May 8, 2015.1 Titled “Perfect Nails, Poisoned Workers,” the article detailed the exploita-tion of these largely immigrant workers and the chronic health effects of near continual exposure to chemicals used in polishes, hardeners, glues, and solvents. The article serves as a flashpoint for awareness of this problem and even resulted in New York Governor Andrew Cuomo declaring emergency measures for this industry that addressed its egregious pay issues and mandated some basic salon worker safety measures. This action should also spur more research into the chemicals and chemical mixtures used in salons and their effects on the women who work there.

While this study found no adverse effects on the children, save the low SGA in Vietnamese women, there were several adverse effects in the women themselves. Risk for gestational diabetes, premature rupture of membranes, and placenta previa were all significantly higher in the cosmetologists and manicurists.

A higher risk of diabetes in those exposed to endocrine-disruptors is not new information. In 2004, the National Health and Nutritional Examination Survey (NHANES) found a similar association.2 The NHANES analyses showed that most participants have detectable blood and/or urine levels of several chemicals, in particular bisphenol A (BPA). Diabetes was strongly associated with exposure to polychlo-rinated biphenyl, dioxins, dichlorodiphenyldichloroeth-

ylene, phthalates, and also BPA (with an OR reaching 2.74; 95% CI:1.44-5.23) after adjusting for age, gender, body mass index, and ethnicity. Salons are rife with endocrine- disruptors, including BPA and phthalates.

As so many of these chemicals are endocrine-disruptors, the increased risk for diabetes is not surprising. It would have been interesting to look for other endocrine disruptions, such as thyroid disease, hormonal perturbations, and congenital abnormalities like hypospadias, since endocrine-disruptors often cause these conditions.

Numerous studies have been focused on the association between endocrine-disrupting chemicals and hypospadias. In a recent study carried out in France, fetal exposure to endocrine-disruptors during the window of genital develop-ment was more frequent in the case of hypospadias (OR:3.13; 95% CI:2.11-4.65).3 Furthermore, hairdressers and beauti-cians were identified, along with cleaners and lab workers, as professionals with the most exposure to these substances, and these women were more frequently the mothers of hypospa-diac boys. In addition, according to the authors of this study, “the types of substances having an impact on the phenotype were heterogeneous, but detergents, pesticides, and cosmetics accounted for 75 percent of the cases.”3 The authors eluci-dated some of the endocrine-disrupting chemicals linked to the professions involved in the study: BPA, phthalates, polychlorinated compounds, alkylphenolic compounds, and organic solvents.

The study being reviewed did not examine miscarriage rates among manicurists and cosmetologists. However, previous studies have found some evidence of both increased rates of miscarriage and time-to-pregnancy in hairdressers.4 In 1 study, female hairdressers were found to have an increased risk of infertility (OR:1.30; 95% CI:1.08-1.55) and an increased risk of spontaneous abortion (OR:1.31; 95% CI:1.07-1.60).5 Others studies failed to find such an associa-tion that reached statistical significance.4

Volatile solvents such as formaldehyde, methacrylates, acetone, xylene, and toluene, as well as parabens and



phthalates, are just some of the chemicals found in these salons. Nail products typically contain the trifecta of toxi-cants: toluene, formaldehyde, and phthalates.6 Some nail polish manufacturers have reformulated their nail polish to be free of the toxic 3. Disturbingly, however, California regulators in 2012 tested 25 randomly chosen nail polishes from 6 distributors that sell to many of the 48,000 salons in California and found the toxic trio in several of the samples chosen. According to the report, 10 of the 12 polishes that claimed to be free of toluene actually contained the substance. Five of 7 products that claimed to be free of all 3 chemicals were found to contain 1 or more of the chemicals at elevated levels.7 It cannot be inferred if the polish labels were delib-erately misleading or if a vendor in the supply chain had misrepresented the chemical makeup of their ingredients unbeknownst to the formulator of the final, finished product.

As with other chemicals that have been found to be detrimental to human health, the “cure” is sometimes illusory and diffi-cult to rely upon. In the case of BPA, BPS and BPF and other analogs used as substitutions have been found to be similarly hormonally active as BPA and also have endocrine-disrupting effects.8 It stands to reason that chemical substitutions for problematic chemicals need to be thoroughly vetted as well.

In a study of occupational urinary phthalate metabolites found across 8 different industries, levels of phthalates in salon workers were found to be twice as high relative to the general population.9 In another study, indoor air was tested for phthalates in homes, offices, laboratories, schools, hair and nail salons, and public places. The highest concentra-tion was found in the salons, at 2,600 ng/m3; the second highest concentration of phthalates was found in the homes, at 732 ng/m3.10 Inhalation is an important exposure route for humans, so these levels bear further study for their health effects. Also, consideration of the contributors to home indoor air that contains high levels of phthalates is warranted when evaluating patients for toxic exposures.

Phthalates have been found to be associated with earlier breast and pubic hair development in girls exposed in the peripubertal timeframe as well as genital variations in infant boys exposed prenatally and neurobehavioral issues in school-age boys.11-13 These findings are concerning because there are often biological responses to the same doses of chemi-cals found in everyday exposure to common household and personal care products.

Solvent exposure poses its own risks. In a recent study that examined pregnant women, including hairdressers, and their occupational exposure to solvents, significant associations were found between major congenital malformations and maternal exposure to solvents—OR:2.48; 95% CI:1.4-4.4 for regular exposure vs no exposure based on self-reporting, which jumped to the occupationally derived solvent matrix result (OR:3.48; 95% CI :1.4-8.4 for highest level of expo-sure vs no exposure). A significant dose-response trend was observed with both assessment levels. The congenital malfor-mations were mainly oral clefts, urinary malformations, and male genital malformations.14

From a clinical perspective, it behooves us to evaluate our manicurist and cosmetologist patients for toxicant body burden. We should elicit information about the chemicals and chemical processes that are suspected of containing endo-crine-disrupting chemicals that have been shown to be associ-ated with poorer pregnancy outcomes and maternal health. Because females of reproductive age make up the majority of this population, awareness of toxicants in their environment can and should be a part of their treatment plan, particularly if these women wish to conceive. More research is needed to understand possible occupational reproductive and other health risks for cosmetologists due to the sheer number of chemical products that they are exposed to on a daily basis. Finally, personal care product safety as a whole needs to be more extensively studied.



REFERENCES1 Maslin Nir S. Perfect nails, poisoned workers. New York Times. May 8, 2015. Avail-

able at:http://www.nytimes.com/2015/05/11/nyregion/nail-salon-workers-in-nyc-face-hazardous-chemicals.html. Accessed August 3, 2015.

2 Chevalier N, Fenichel P. Endocrine disruptors: New players in the pathophysiology of type 2 diabetes? Diabetes Metab. 2015;41(2):107-115.

3 Kalfa N, Paris F, Philbert P et al. Is hypospadias associated with prenatal exposure to endocrine disruptors? A French collaborative controlled study of a cohort of 300 consecutive children without genetic defect. Eur Urol. 2015 May 23; pii:s0302-2838(15):0409-1.

4 Axmon A, Rylander L, Lillienberg L, Albin M, Hagmar L. Fertility among female hair-dressers. Scand J Work Environ Health. 2006;32(1):51-60.

5 Baste V, Moen BE, Riise T, Hollund BE, Oyen N. Infertility and spontaneous abor-tion among female hairdressers: the Hordaland Health Study. J Occup Environ Med. 2008;50(12):1371-1377.

6 Quach T, Doan-Billing P, Layefsky M et al. Cancer incidence in female cosmetologists and manicurists in California, 1988-2005. Am J Epidemiol. 2010;172(6):691-699

7 Environmental Working Group. Calif. Regulators: “Non-Toxic” Nail Polishes Anything But. April 10, 2012. Available at:http://www.ewg.org/news/news-releases/2012/04/10/calif-regulators-%E2%80%9Cnon-toxic%E2%80%9D-nail-polishes-anything. Accessed August 3, 2015.

8 Rochester JR, Bolden AL. Bisphenol S and F: a systemic review and comparison of the hormonal activity of bisphenol A substitutes.Environ Health Perspect. 2015;123(7):643-650.

9 Hines CJ, Nilsen Hopf NB, Deddens JA, et al. Urinary phthalate metabolite concentra-tions among workers in selected industries; a pilot biomonitoring study. Ann Occup Hyg. 2009;53(1):1-17.

10 Tran TM, Kannan K. Occurrence of phthalate diesters in particulate and vapor phases in indoor air and implications for human exposure in Albany, New York, USA. Arch Environ Contam Toxicol. 2015;68(3):489-499.

11 Wolff MS, Teitelbaum SL, Pinney SM, et al. Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols, and pubertal stages in girls. Environ Health Perspect. 2010;118(7):1039-1046.

12 Kobrosly RW, Evans S, Miodovnik A, et al. Prenatal phthalate exposures and neurobe-havioral development scores in boys and girls at 6-10 years of age. Environ Health Perspect. 2014;122(5):521-528.

13 Ormond G, Nieuwenhuijsen MJ, Nelson P, et al. Endocrine disruptors in the workplace, hairspray, folate supplementation, and risk of hypospadias: case control study. Environ Health Perspect. 2009;117(2):303-307.

14 Garlantezec R, Monfort C, Rouget F, Cordier S. Maternal occupational exposure to solvents and congenital malformations: a prospective study in the general popula-tion. Occup Environ Med. 2009;66(7):456-463.

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PRACTICE IMPLICATIONSThere is an axiom in toxicology that “the dose makes the poison.” The implication is that a chemical is innocuous until some threshold dose is reached, at which point it can have toxic effects. When considering carcinogens, this is useful for single agents that have proven thresholds (eg, arsenic, asbestos). This type of direct dose-related effect allows for classification of chemicals by carcinogenic potential.2 This singular dose-determined carcinogenic potential is relevant for occupational exposures, contaminated land/water, and other high-dose exposure scenarios.

However, what if there is synergistic carcinogenic potential resulting from hundreds of low doses of chemicals that are going unnoticed? What if dozens of chemicals work together on multiple molecular pathways to culminate in carcinogenesis? These are very practical questions given that such exposures are the reality of our everyday existence. They are also of great relevance because cancer is a close second only to heart disease as the most common cause of death in the United States.3 Given these consider-ations, such questions should take on immediacy in toxicology research. However, the dominant paradigm is still based on the old axiom “the dose makes the poison.”

What if there is synergistic carcinogenic potential resulting from hundreds of low doses of chemicals that are going unnoticed? What if dozens of chemicals work together on multiple molecular pathways to culminate in carcinogenesis?

The government-funded Agency for Toxic Substances and Disease Registry (ATSDR) has taken a stance on the role of ubiquitous chemicals and cancer causation in its publication Chemicals, Cancer and You.4 In it, the ATSDR notes, “More than 100,000 chemicals are used by Ameri-cans, and about 1,000 new chemicals are introduced each year. These chemicals are found in everyday items, such as foods, personal prod-ucts, packaging, prescription drugs, and household and lawn care prod-ucts.” Later in the same document is a disconcerting disconnect between these facts and ATSDR’s conclusion that “[t]hese everyday exposures are usually too small to cause health problems.” This, of course, is the old axiom of toxicology at work.

ATSDR is an official agency whose purpose is to “increase knowledge about toxic substances, reduce the health effects of toxic exposures, and protect the public health.” Pervasive throughout its official publications is the notion that carcinogens are singular substances deemed to cause cancer at some

REFERENCEGoodson WH 3rd, Lowe L, Carpenter DO, et al. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis. 2015;36 Suppl 1:S254-S296.

DESIGNEleven teams of international toxicologists and biologists reviewed relevant data on ubiquitous chemicals and their possible influence on carcino-genesis based on the “hallmarks of cancer.”1 Each team was to determine “prototypical” chemicals that are involved in the given hallmark. The 11 teams were assigned to these categories: angio-genesis, dysregulated metabolism, evasion of antigrowth signaling, genetic instability, immune system evasion, replicative immortality, resistance to cell death, sustained proliferative signaling, tissue invasion and metastasis, tumor microenvi-ronment, and tumor-promoting inflammation.

Each team was tasked with determining chemical compounds that affect the given pathway and are (1) ubiquitous in the environment, (2) not known carcinogens, (3) not “lifestyle”-related (eg, fried foods, smoking), and (4) “selectively disruptive” to the assigned hallmark of cancer. The teams were further tasked to determine the level of exposure necessary to elicit effects on the given pathway and whether a linear or nonlinear relationship to the given chemical’s action exists.

KEY FINDINGSIn total, 85 chemicals were deemed prototypical disruptors of 1 or more hallmarks of cancer. Fifty out of the 85 chemicals (59%) exerted low-dose effects (“at levels that are deemed relevant given the background levels of exposure that exist in the environment”). Fifteen of these 50 had a nonlinear dose-response pattern. Thirteen of the 85 prototypical agents (15%) had a dose-response threshold. Twenty-two of the 85 agents (26%) lacked sufficient information to define any dose-response relationship.


Low-dose Chemical Mixtures as CarcinogensThe effects of multiple toxins on the human body, and what it means for the future of healthcare By Tina Kaczor, ND, FABNO



threshold dose.5 The conclusion that combinations of low levels of chemicals are harmless is based on a lack of research, not research suggesting safety of chemical mixtures. As the adage goes, “the absence of evidence is not evidence of absence.”

The paper reviewed here posits a means to systematically study the effects of multiple chemicals that more realistically mimics current environmental exposures. It is, essentially, a paradigm shift. Using the “hallmarks of cancer” as the framework to understand the various attributes of chemicals in relation to cancerous processes, research can investigate common environmental chemicals and discern whether a chemical affects a given pathway(s) and at what dose. This leads to a better understanding of synergistic effects on carci-nogenic processes, even by chemicals considered noncar-cinogens as single agents.

Of the 85 chemicals that were found to affect key pathways related to carcinogenesis, only 15% (13/85) were found to have a dose-response threshold, the classic dose threshold model of toxicity. Low-dose effects were predominant in 59% (50/85) of the compounds. The authors concluded, “Our analysis suggests that the cumulative effects of indi-vidual (non-carcinogenic) chemicals acting on different path-ways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies.”

Some of the chemicals found to disrupt key pathways that contribute to the various hallmarks include bisphenol A (BPA), phthalates, nickel, cadmium, diazinon, and mala-thion. Avoidance of chemical ingestion—whether from water, air, or food—is clearly the wisest option. Unfortu-nately, it is not a feasible option given the ubiquity of chemi-cals in our environment.

The paper under review was not a small undertaking. It is a result of an ambitious project that began with a consortium of scientists from many disciplines that first met in Halifax, Nova Scotia, in 2013. The meeting was hosted by the orga-nization Getting to Know Cancer. The mission statement for Getting to Know Cancer is “To share holistic, scientific knowledge about cancer with key stakeholders who have an

interest in the disease in a manner that ultimately results in societal changes that reduce the public exposure to disrup-tive environmental agents that can act in concert with one another to instigate cancer.”6 The gathering was sponsored by the National Institute of Environmental Health Science, a division of the National Institutes of Health.

The consortium continues its ongoing work to lay the foun-dation for this emerging concept, namely the “low-dose carci-nogenesis hypothesis.” Perhaps the authors best summarize the utility of the paper reviewed here:

The chemicals that were selected for this review were not deemed to be the most important, and they were not selected to somehow imply (based on current information) that they are endangering us. Rather, we simply wanted to illustrate that many non- carcinogenic chemicals (that are ubiquitous in the environment) have also been shown to exert effects at low doses, which are highly relevant to the process of carcinogenesis.

EDITOR’S NOTEThe article reviewed here is not a clinical trial; it is a paper written by a consortium of scientists who looked at the evidence for carcinogenic potential of commonly used chemi-cals. We normally review only studies using human data in the Abstracts & Commentary section, but since this is such important work and represents a paradigm shift, the editorial team made an exception.

REFERENCES1 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):

646-674.

2 World Health Organization. Agents classified by the IARC monographs, volumes 1-113. Available at:http://monographs.iarc.fr/ENG/Classification/. Accessed August 28, 2015.

3 US Centers for Disease Control and Prevention. Faststats: Leading causes of death. Available at: http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Updated August 21, 2015. Accessed August 28, 2015.

4 Agency for Toxic Substances and Disease Registry, Division of Health Assessment and Consultation. Chemicals, Cancer, and You. Available at: http://www.atsdr.cdc.gov/emes/public/docs/Chemicals,%20Cancer,%20and%20You%20FS.pdf. Accessed August 28, 2015.

5 US Department of Health and Human Services, National Toxicology Program. Definition of carcinogenicity results. Available at: http://ntp.niehs.nih.gov/results/pubs/longterm/defs/index.html. Accessed August 28, 2015.

6 Getting to Know Cancer. Mission. Available at: http://www.gettingtoknowcancer.org/visionmission.php. Accessed August 28, 2015.


REFERENCESolimini AG, D’Addario M, Villari P. Ecological correlation between diabetes hospitalizations and fine particulate matter in Italian provinces. BMC Public Health. 2015;15(1):708.

DESIGNCross-sectional data were aggregated from Italian institutional and regional databases from 2008 through 2010 to determine correlations between hospital discharges with diabetes and fine partic-ulate matter (PM2.5) levels, adjusting for common risk factors and socioeconomic factors.

DATAThe data cover 48 Italian provinces, with a popu-lation of more than 34 million residents (60% of the total Italian population). The particulate matter up to 2.5 micrometers in size (PM2.5) average levels between 2008 and 2010 in the Italian provinces ranged between 11 μg/m3 to 32 μg/m3 with a mean of 20.1 μg/m3. Diabetes hospital discharge in patients older than 45 years ranged for women between 4.6 to 66.9 per 10,000 with a mean of 16.2; the range for men was between 8.4 and 83.8 per 10,000 with a mean of 23.4.

PARTICULATE MEASURESAnnual levels of PM2.5 of Italian cities were obtained in hourly measurements from moni-toring stations belonging to regional networks. The time period and the monitoring stations were chosen to match the hospital discharge data at the provincial level.

KEY FINDINGSDiabetes hospitalizations increased with increased annual PM2.5 concentrations, with a rise of 3.5% (1.3%-5.6%) for men and of 4.0% (1.5%-6.4%) for women per μg/m3 of PM2.5 increase.

PRACTICE IMPLICATIONSThis paper suggests that controlling exposure to air pollution may reduce incidence of diabetes and complications (in particular, hospitalizations) for diabetics. This is a connection that few practitioners think of when working with this patient population. While we are well aware that what and how much we eat impacts weight, metabolic syndrome, and diabetes, these 2 factors do not take into consideration how well we process calories. Increasing evidence shows that overexposure to environmental toxins from all sources can negatively affect human metabolic pathways.

At least 5 cohort studies have sought an association between air pollution and type 2 diabetes. Krämer reported in 2010 that traffic-related air pollu-tion was associated with incident type-2 diabetes among elderly women in the industrialized Ruhr region of Germany.1 A 2013 study that examined a cohort of more than 60,000 people in Ontario, Canada, reported an 11% increase in diabetes incidence per 10 µg/m3 increase in PM2.5.2


Air Pollution Aggravates DiabetesStudy links particulate matter levels and diabetes-related hospitalizations

By Julianne Forbes, ND, and Jacob Schor, ND, FABNO


http://naturalmedicinejournal.com/special-issues


This study contrasts a report published in 2012 that, while finding a 25% increase in diabetes with interquartile increases in nitrogen dioxide (NO

2) in a cohort of black women living

in Los Angeles, did not find an association between diabetes and fine particulates.3 Two other US prospective cohorts also failed to find associations with diabetes and PM2.5 or PM10, yet they did find an association with “distance to road,” a stand-in marker for traffic-related pollution.4 In Denmark, Andersen et al found a borderline statistical association between confirmed cases of diabetes and NO

2 levels.5 Pearson

et al in 2010 reported a 1% increase in diabetes with an increase by 10 µg/m3 of PM2.5.6

This current Italian study suggests a greater risk increase than Pearson, a 35% increase for men and a 40% increase for women per 10 µg/m3 PM2.5. We should note that Pearson’s

cohort was exposed to lower PM2.5 concentrations—2.5 µg/m3 to 17.7 µg/m3 (median=11 µg/m3)—compared to the people in this Italian study, whose exposure was 11 µg/m3 to 32 µg/m3 with a higher median equal to 8.68 µg/m3.

Mechanisms exist to explain a possible association, in partic-ular that the air pollutants increase systemic oxidative stress and trigger inflammatory changes that lead to insulin resis-tance.7,8 In animals, exposures to persistent organic pollutants are consistently associated with insulin resistance and type 2 diabetes.9 In addition, a review outlined how toxins can provoke insulin resistance through debilitated thyroid func-tion and mitochondrial injury.10

Several studies now suggest that indoor air filtration systems, by reducing PM2.5 levels, also decrease markers of cardiovas-cular disease risk.11,12 Using the same manner of intervention, cleaning indoor air via filtration may potentially prove useful in treating insulin resistance, lowering incident diabetes, and reducing risk of diabetic complications and hospitalizations.

REFERENCES1 Krämer U, Herder C, Sugiri D, et al. Traffic-related air pollution and incident type 2 diabetes:

results from the SALIA cohort study. Environ Health Perspect. 2010;118(9):1273-1279. 2 Chen H, Burnett RT, Kwong JC, et al. Risk of incident diabetes in relation to long-

term exposure to fine particulate matter in Ontario, Canada. Environ Health Perspect. 2013;121(7):804-810.

3 Coogan PF, White LF, Jerrett M, et al. Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation. 2012;125(6):767-772.

4 Puett RC, Hart JE, Schwartz J, Hu FB, Liese AD, Laden F. Are particulate matter expo-sures associated with risk of type 2 diabetes? Environ Health Perspect. 2011;119(3):384-389.

5 Andersen ZJ, Raaschou-Nielsen O, Ketzel M, et al. Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes Care. 2012;35(1):92-98.

6 Pearson JF, Bachireddy C, Shyamprasad S, Goldfine AB, Brownstein JS. Asso-ciation between fine particulate matter and diabetes prevalence in the U.S. Diabetes Care. 2010;33(10):2196-2201.

7 Xu X, Liu C, Xu Z, et al. Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicol Sci. 2011;124(1):88-98.

8 Sun Q, Yue P, Deiuliis JA, et al. Ambient air pollution exaggerates adipose inflam-mation and insulin resistance in a mouse model of diet-induced obesity. Circula-tion. 2009;119(4):538-546.

9 Rajagopalan S, Brook RD. Air pollution and type 2 diabetes: mechanistic insights. Diabetes. 2012;61(12):3037-3045.

10 Hyman M. Systems biology, toxins, obesity, and functional medicine. Altern Ther Health Med. 2007;13(2):S134-S139.

11 Chen R, Zhao A, Chen H, et al. Cardiopulmonary benefits of reducing indoor particles of outdoor origin: a randomized, double-blind crossover trial of air purifiers. J Am Coll Cardiol. 2015;65(21):2279-2287.

12 Weichenthal S, Mallach G, Kulka R, et al. A randomized double-blind crossover study of indoor air filtration and acute changes in cardiorespiratory health in a First Nations community. Indoor Air. 2013;23(3):175-184.



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