Health+Effects+associated+with+PBDE's


 * Health Concerns Associated with PBDEs**

The affect of PBDE exposure has been in question since the 1990’s. PBDEs are often leached from products and released into the ecosystem (Chao et al, 2010). The biggest issue is that PBDEs are known to bioaccumulate in blood, breast milk and fat tissues of organisms. PBDEs are known to be lipophilic endocrine disruptors (Darnerud et al, 2001) as well as persistent organic pollutants (POPs) (Chao et al, 2010). Health effects include cancer, thyroid problems and neurological consequences (Schmidt, 2003; Eriksson et al, 2004). A detrimental concern with decaBDE arises because it is virtually nontoxic under laboratory conditions, however in a natural environment, it is broken down into pentaBDE and tetraBDE forms, which then bioaccumulate (Schmidt, 2003). Europe appears to see the highest levels in the environment nonetheless, levels are on the rise worldwide (Health Canada, 2009). Another huge concern is PBDEs as allergens. PBDEs are showing up in the households at alarming levels, mostly in the form of dust. DecaBDE has yet to be removed even though it was proven to be toxic and can breakdown into further harmful forms and has been found to be the predominant PBDE in houses. The problem is that the release of PBDEs from products are higher than expected and is a great risk of direct exposure to humans especially in the form of dust which is inhaled on a daily basis. (Environmental Working Group, 2008).


 * PBDEs in Food Markets**

It has been proven that high levels of PBDEs are now found in our food supply. They are very similar to polychlorinated biphenyls which where the concern comes in. The latter has recently decreased in blood levels but PBDEs have substantially increased over the last 2-3 decades. The actions of the congeners vary due to physical, chemical, and biological properties. Its effects in humans aren’t definite but animal studies have proven reproductive and developmental toxicity, endocrine disruption, cancer and central nervous system (CNS) effects. An experiment using mass spectrometry was used to measure basic food items from three major supermarkets in Dallas. These items included fresh and processed meats, fish, milk products, and eggs. The results showed that the highest concentrations of PBDEs were found in fish, followed by meats and dairy. Considering the average American’s diet, meat is highly consumed, so this is where the major problem lies. (McGovern, 2006)


 * 2.4 PBDEs in Breast Milk**

Research in animals shows that exposure to brominated fire retardants in-utero or during infancy leads to more significant harm than exposure during adulthood, and at much lower levels. Again the concern is the similarity between PBDEs and PCBs which can sometimes act in concert with one another increasing their levels of contamination. Much of the known effects are due to the damage of thyroid hormones T3 and T4 - both of which regulate metabolism. Hypothyroidism affects foetuses and infants differently than adults: for a fetus, low levels of T4 result in an IQ lower than 85. Some cases can be as low are 70, mild retardation.

Studies were done over a short period of time (14 days or less) but it’s been proven that more damage is done with lower dosages over a long period of time. So what about just one dosage at a critical point in brain development? In two different studies, a small dose — as little as 0.8 mg/kg-day — given to 10-day-old mice caused "deranged spontaneous behavior," significant shortfalls in learning and memory and reduced ability to adapt to new environments, with these problems often becoming more pronounced with age (Environmental Working Group, 2008). No effects were seen at a later stage with the same dosage of PBDEs in the brain.

It’s not fully clear yet how PBDEs affect neurological development but some theories have been constructed; PBDEs mimic thyroid hormones, increase their clearance in the body and interfere with intracellular communication. In-utero exposures have also been associated with serious harm to the fetus, including limb and ureter malformation, enlarged hearts, bent ribs, fused stemebrae, delayed bone hardening, and lower weight gain (Environmental Working Group, 2008). There have been few studies on the effects of organ structure but evidence has shown that low doses (10 mg/kg-day) can cause thyroid tissue overgrowth, enlarged livers and changes in the cell structure, abnormal cell functioning, localized cell death and deformation in the kidney. Only one PBDE has been tested as a cancer causing agent- Deca-BDE- it’s the least easily absorbed and the most rapidly eliminated. The concern lies in the fact that congeners can cause cell recombination which then increases the urge to look at congeners with a lower bromine count. (Environmental Working Group, 2010).


 * 2.5 Bioaccumulation of PBDEs**

As with any synthetic organic, the possibility for accumulation within the environment and subsequently within the body is a major concern. PBDEs were extensively studied in the early millennia and found to accumulate considerably, both in the environment and within many different stages in the food chain at varying quantities. As stated above PBDEs have the ability to accumulate because of their high lipophilicity and their resistance to degradative processes (Boer et al, 1998). The half lives of PBDEs vary due to the presence of over 200 congeners however all PBDEs of concern posses half lives of >2 days, 2 months and 6 months in air, water and soil respectively (Birnbaum et al, 2004). Considering the resilience of these flame retardants and the production of upwards of 67,000 tonnes annually establishes a serious cause for concern. In aquatic life, significant PBDE levels have been discovered in everything from shallow dwelling fish (bass and carp) to deep feeders such as sperm whales (Boer et al, 1998). The exposure of sperm whales to PBDEs is of particular concern as they feed at depths up to 3 kilometres deep (Gaskin et al, 1966) indicating the extent of the environmental contamination by these retardants. It is no surprise that contamination in land mammals as well as humans has also proliferated over the last 20 years, with ever increasing levels. PBDE levels in breast milk lipids in women from Sweden increased from about 1ng/g fat in 1990 to 3.5ng/g fat in 2000 (Lind et al, 2003). The same study concluded that almost 50% of the PBDEs found in the breast milk lipids were ingested by the eating of fish. To put this in perspective Osprey (high fish diet) in Sweden were found to have PBDE content in their muscles of up to 2100ng/g (DeWit, 2010).

It is important to realize that all PBDEs do not absorb or bioaccumulate to the same extent among differing species. However, BDE-47 is almost universally the most accumulated among mammals.

Within breast milk the average amount of BDE-47 found in breast milk was 2.35ng/g where as the next most abundant congener had an average of 0.68ng/g (Lind et al, 2003). Although BDE-47 is the most accumulated amongst most mammals, fish demonstrate a wide variety of compositions which range from having 47% BDE-47 to 17%. The regulation of these PBDEs is a complex matter due to decomposition and accumulation along with ease of manufacture. This is why the safest way to regulate these complex toxins is to completely ban them which is an ongoing process due to their high effectiveness in both cost and function.


 * 2.6 Hepatocyte Metabolism of PBDEs**

In a study, Hepatocytes were exposed to two common congeners (BDE-209 and BDE-99) for 24-72 hours to see if they would be metabolized and what metabolites would be formed. After 48 hours, the mass of each BDE was recorded. The more BDE recovered the less the PBDE was metabolized. It was discovered that less BDE-99 was recovered as well as the presence of metabolites and therefore metabolized further than BDE-209. Upon examining metabolites it was apparent that reductive debromination is not likely to be a substantial metabolic pathway in human liver tissue since there were no reductively debrominated metabolites. Upon looking at oxidative metabolites, none were found for BDE-209 based on the hypothesis that the intermediates that formed bound to BDE-209 and therefore weren’t recovered. In contrast, BDE-99 had four oxidative metabolites in all hepatocytes that were exposed. The first, a tribromophenol, analyzed to be 2,4,5-tribromophenol. Metabolites 3 and 4 were identified as ethyl derivative of mono-OH-pentabrominated diphenyl ethers (Br5-MeO-BDE and 5′-MeO-BDE-99) and were found at levels 2-3 times higher than 2,4,5- tribromophenol. Metabolite 2 was not positively identified but likely contained four bromines, as well, exposure studies with rats and mice have identified oxidative debrominated after exposure to BDE-99 //in vivo// therefore, it is possible that metabolite 2 is a tetra-OH-BDE. (Stapleton et al, 2009).


 * 2.8 Dioxins**

Plastics that have been treated with PBDEs have a much denser and toxic smoke than that produced from plastics without them (Webster, 2009). This is because when PBDEs are burned they release dioxins, such as polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), in their combustion (Mousavi et al, 2009). Dioxins are toxic and carcinogenic chemicals and exposure has been shown to have many negative effects on health (Mousavi et al, 2009). One of the most common ways that PBDEs are destroyed by fire is through the burning of products containing them at waste sites. This is most significantly seen in developing countries, such as Mexico, which frequently burn waste to reduce its volume (Gullett et al, 2010). When these chemicals become airborne they are capable of attaching to small particles, attributing to their capability of traveling long distances (Health Canada, 2005). Like PBDEs, dioxins and furans can be stored in fat and therefore can be spread through the food-chain by bioaccumulation (Health Canada, 2005).

Human exposure to dioxins is known to produce some types of cancer, skin disorders, liver problems, impairment of the immune system, and to affect the developing nervous system (DeVito, 2007). There have been several studies linking dioxin to soft-tissue sarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma, as well as stomach, nasal, and liver cancer (Fingerhut et al, 1991). However, there has been much debate over the danger of PBDEs, with some suggesting that there is no direct evidence that flame retardants do in fact cause these health risks (Landry, 2003). Cancer is one of the greatest public concerns in regards to dioxin exposure, but is very difficult to study effectively. A group of subjects exposed to these toxins may not show any symptoms until 20 years later. Despite this uncertainty many firefighting organizations, with the objection of reducing chemical exposure to their workers, are in support of banning PBDEs. Firefighters are most notably at risk of exposure to dioxins, which can be inhaled or settle on equipment (Webster, 2009).




 * 2.9 Neonatal Imprinting and other developmental defects from PBDEs or substitute fire-retardants containing phthalates or bisphenol A**

Estrogens are implicated in the normal development of the stromal portions of hormonally sensitive tissues, such as the male prostate gland. A relative excess of estrogen activity during the gestation period can lead to permanent perturbations in the activity of important regulatory genes that determine shape and structure of tissues involved in reproduction. This process is called neonatal imprinting or developmental estrogenization. These neonatal exposures to excess estrogen are associated with increased incidence of prostate, breast and uterine diseases associated with aging, such as hyperplasia, inflammation, and neoplasia. It is hypothesized that molecular changes brought about by early exposure to excess estrogen activity can predispose the tissues regulated by estrogen into a neoplastic state (cancer) upon aging1.

Estrogen amplifies its own effects through auto up-regulation of its own receptor, and also the aromatase enzyme2. The aromatase enzyme is responsible for catalyzing testosterone and other ring-A oxidized androgens into estrogens, thus compounding the activity. Such up-regulation can begin a positive feedback situation, where the tissue sensitivity to estrogen may be permanently altered due to previous estrogen exposures. Tissue sensitivity to estrogens has also been implicated in diseases such as breast and ovarian cancers, male gynecomastia, male birth defects, and sub-normal fertility. The sub-normal fertility may manifest itself in the offspring of the female animal originally exposed.3, Estrogen activity has been associated with altered subcutaneous fat-depot storage via up-regulation of α1a adrenoceptors on adipocytes, leading to localized hypertrophy of gender-specific fatty deposits.

The polybrominated diphenyl esters (PBDE’s) have been long associated with having estrogenic activities. The tetrabrominated and hexabrominated derivatives have both been reported as estrogenic3,4. The earlier reference dates to the early 1980’s where exposure to ¼ gram daily doses of PBDE to pregnant cattle resulted in offspring that had difficulty conceiving additional calves, even though the offspring were no longer dosed with any further PBDE’s after birth. The more recent experiments with tetrabrominated PBDE derivatives have attempted to measure the induction of the estrogen-dependent gene-product calbindin-D9k as a result of exposure to PBDE’s. The calbindin-D9k can serve as a biomarker for estrogen exposure in the immature female rat, and correlates with estrogen-induced uterine hypertrophy. It is also interesting to note that both effects of calbindin-D9k induction and uterine overgrowth can both be substantially reversed by co-administration of an estrogen receptor antagonist. Both studies strongly suggest that PBDE’s are endocrine disruptors.

Male neonatal exposure to some phthalates has been implicated in demasculinizing the newborn boy. High levels of phthalates in pregnant women's urine are correlated to greater problems in infants. The incidence of hypospadia has increased three-fold in the past 30 to 40 years, and the incidence of un-decended testicle has increased about two-fold. There are also studies that link phthalates to low sperm counts and low testosterone levels in adult men.6,7,8,9


 * 2.10 Effects of phthalates on the clonal expansion of adipocytes**

The phthalates are also implicated as activating peroxisome proliferator activated receptors (PPAR).10 The PPAR-γ receptor subtype is present in muscle and fatty tissue where it plays a role in repartitioning digested food into lean tissue and adipose. The term proliferator refers to the actions these receptors have to initiate clonal expansion of adipose and other cells. Clonal expansion of adipose implies there will be more adipose cells available to store triglycerides, thus promoting a bias towards permanent subcutaneous obesity. Adipose tissue hypertrophy can perhaps be partially addressed by diet and exercise however adipocyte hyperplasia is very often refractory to practical slimming attempts.

Considering that substitute fire-retardant ring-brominated benzoates, and other fire-retardants are made from brominated phthalates or brominated bisphenol A, there is a disturbing question if the replacement fire-retardants are also capable of endocrine-disruption. It may be possible to evaluate these or other compounds for estrogen-like or peroxisome proliferator-activated retinoid activities with a bioassay. It is important to note that not all phthalates or other polymer additive molecules will exhibit an apparent endocrine-disrupting action.11 Each separate polymer additive should be screened against all known endocrine, paracrine, autocrine or other cell-to-cell signaling mechanism before it can be called ‘safe’.

It would presently be difficult to conclusively implicate common diseases experienced later in life to early excess exposures to the endocrine-disrupting activities of PBDE, bisphenol, or phthalate derivatives. It is obvious that obesity and reproductive problems plague modern society, and some incidence of these diseases would still be expected even in absence of these polymer additives. Nevertheless, it is worrisome to consider the possibility, especially since prostate hyperplasia, adipocyte hyperplasia, breast or prostate neoplasia, and male gynecomastia are all common complaints in industrial societies. The end treatments for each of these specific conditions can involve surgical or other interventions which may negatively impact overall quality of life. In some cases, current medical technologies are insufficient to reliably repair the possible consequences initiated by a poorly regulated endocrine system. About half of all gynecomastia reduction surgeries result in complications 12,13,14 Due to the morbidity and suffering associated with these relatively common diseases, it is important to monitor the state of the endocrine system to minimize irreparable harm. To the extent that excessive exposure to exogenous endocrine-disrupting agents can unfavorably initiate disease, it is important to characterize, watch for, and minimize extraneous exposures to known endocrine-disrupting substances.

Endocrine-disruption definition:

Weybridge definition (1996): “An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism, or its progeny, secondary to changes in endocrine function.”

IPCS definition (2002): “An endocrine-disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.”

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1The Role of Estrogens in Normal and Abnormal Development of the Prostate Volume 1089 Issue Estrogens and Human Diseases Pages 1-13 Gail S. Prins, Liwei Huang, Lynn Birch and Yongbing Pu Endocrinology 1997 138: 1801-1809,

2 Estrogen receptor-related receptor alpha mediates up-regulation of aromatase expression by prostaglandin E2 in prostate stromal cells Miao L, Shi J, [|Wang CY], [|Zhu Y], [|Du X], [|Jiao H], [|Mo Z], [|Klocker H], [|Lee C], [|Zhang J]., Mol Endocrinol. 2010 Jun; 24(6):1175-86

3Estradiol Up-Regulates Estrogen Receptor and Progesterone Receptor Gene Expression in Specific Ovine Uterine Cells' Nancy H. lng, and M. Belen Tornesi, Biology of Reproduction, 56, 1205-1215 (1997)

4Performance and Health of Offspring of Cows Experimentally Exposed to Polybrominated Biphenyls L. B. Willett, H. I. Durst, T-T. Y. Liu, F. L. Schandbacher and P. D. Moorhead. 1982 J Dairy Science 65:81-91

5 Tetrabromodiphenyl Ether (BDE 47) Evokes Estrogenicity and Calbindin-D9k Expression through an Estrogen Receptor-Mediated Pathway in the Uterus of Immature Rats Vu Hoang Dang, Kyung-Chul Choi, and Eui-Bae Jeung Toxicological Sciences 97(2), 504-511 (2007)

6Report on Public Health Concerns – Phthalates and Bisphenol A: Plain Language Summary EPA report_on_phthlalates+bpa.pdf

7C.B.S. “60 Minutes' television documentary, May 23, 2010 with correspondent Lesley Stahl Phthalates: Are They Safe? Chemicals Are Found in Soft Plastic Products We Use Every Day Dr. Shanna Swan, epidemiologist, University of Rochester Medical School Dr. Howard Snyder, pediatric urologist, Children's Hospital Philadelphia

8Time Magazine Top 10 Common Household Toxins April 1, 2010 by Alice Park on a list of 10, decabromodiphenol Ether is #9, phthalates are #5, and bisphenol A is #1

9Testimony: to U.S. House of Representatives, Tuesday June 10, 2008 by Dr John Bucher, Associate Director National Toxicology Program, National Institutes of Health, USA http://www.hhs.gov/asl/testify/2008/06/t20080610a.html

10PPAR-mediated activity of phthalates: A link to the obesity epidemic? Beatrice Desvergne, Jerome N.Feige, and Cristina Casals-Casas. Molecular and Cellular Endocrinology. Vol. 304, Issues 1-2, 25 May 2009, pages 43-48.

11Hallmark.pdf DINP and DIDP are not endocrine-disruptors Second Meeting of the Chronic Hazard Advisory Panel on Phthalates European Council for Plasticisers and Intermediates Nina Hallmark ECPI Technical Working Group U.S. Consumer Products Safety Commission July 26, 2010 [|www.ecpi.org] [|http://www.dnip-facts.com] ad [|http://www.didp-facts.com]

12 Minimally invasive surgical therapy of gynecomastia: liposuction and exeresis technique. Voigt M, Walgenbach KJ, Andree C, Bannasch H, Looden Z, and Stark GB. Chirurg. Oct;72(10):1190-5 (article in German)

13Indications for and results of surgical therapy for male gynecomastia // The American Journal of Surgery ////,// Volume 178, Issue 1, Pages 60-63 M.Colombo-Benkmann

14Gynecomastia: complications of the subcutaneous mastectomy. Steele SR, Martin MJ, Place RJ. Am Surg 2002 Feb;68(2):210-3

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