Wednesday, July 31, 2013

Flame Retardants (PBDEs) and Hyperthyroidism in Cats

Decabromobiphenyl, Polybrominated Diphenyl Ethers, and Brominated Phenolic Compounds in Serum of Cats Diagnosed with the Endocrine Disease Feline Hyperthyroidism

J Norrgran, B Jones, N.G. Lindquist, A. Bergman

Hyperthyroidism is the most common endocrine disorder of cats and is a frequently diagnosed disease in small animal practice. However, despite the high rate of this disease in cats (over 10% of cats older than 10 years of age), hyperthyroidism is a new disease that was first described in only 1979 (1). The sudden appearance and subsequent increase in the prevalence of this disorder has prompted numerous epidemiology studies searching for a potential underlying cause(s). Although such investigations point to a number of environmental and nutritional factors that could play a role in the pathogenesis of this disorder, the underlying causes remain unclear (2,3).

One group of environmental chemicals that may contribute to thyroid disease in man includes the polybrominated diphenyl ethers (PBDEs), synthetic brominated compounds used as flame retardants in a variety of consumer products such as electronics, furniture, textiles, and construction materials.

Because PBDEs are known thyroid disruptors, these chemicals may play a role in the pathogenesis of thyroid tumors and hyperthyroidism in cats. In 2007, Dye et al. published an article regarding a potential link between feline hyperthyroidism and increased concentrations of brominated flame retardants (i.e., polybrominated diphenyl ethers; PBDEs) in cat serum (4). The origin of their hypothesis was the observation of a rapidly increasing number of cats with hyperthyroidism after the late 1970s, concomitant to the introduction and increasing use of brominated flame retardants in household materials (5).

These PBDEs are used as additives, i.e., they have not been chemically bonded into the products. Consequently, over time these chemicals migrate out of the flame-protected materials, e.g., plastics, textiles, furniture, or electronics, and end up in house dust as the natural sink (6,7). Pet cats living indoors, lying down on the floor, and collecting dust in their fur will ingest these dust-enriched chemicals because of their natural behavior of licking when cleaning. For that reason, cats may be highly exposed to PBDEs, even more so than human adults. In accord with this, a number of different investigators in different countries have reported that pet cats tend to have high serum levels of a number of PBDEs (4, 8-11).

The purpose of this study by Norrgran et al (12) was to extend the identification of brominated compounds in cat serum and focus on the hydroxylated metabolites of PBDE. The goal was to investigate various PBDE metabolites to improve our understanding of how cats metabolize these compounds.

Materials and methods— A pooled serum sample (16 ml) was collected from 30 client-owned Swedish pet cats. These cats had all been diagnosed with hyperthyroidism on the basis of finding high serum total T4 concentrations. This pooled serum sample was analyzed for PBDE congeners, and various brominated species were identified and characterized.

Results— The results showed exposure to the discontinued flame retardant decabromobiphenyl (BB-209) and technical penta- and octa-BDEs. Altogether 12 PBDE congeners were identified along with 2'-MeO-BDE68. Furthermore, 2,4-dibromophenol, 2,4,6-, 2,4,5- and 2,3,4-tribromophenol plus 2'-OH-BDE68, 6-OH-BDE47, 5-OH-BDE47, 4'-OH-BDE49 were identified. 2,4,6-tribromophenol and 6-OH-BDE47 were the most prominent species in cat serum.

Conclusions—Considering that these are natural products, it can be concluded that metabolism of PBDEs to OH-PBDEs is not a major route of PBDE elimination in cats. It is notable that the finding of high concentrations of the PBDEs BB-209, 6-OH-BDE47, and 2,4,6-tribromophenol suggest that the body burden of these endocrine-disrupting chemicals are high in Swedish cats.

In my view, the most interesting result in the present study was the high levels of PBDEs in cat serum. The serum PBDE levels in Swedish cats were about 50 times higher than in the general Swedish human population (10,12). Similarly, the serum levels of the PBDEs in cats from the USA were about 20-100 times higher than in the general human US population (4,8).

The results of this study indicate that the metabolism of PBDEs in cats is different and/or slower compared with what is known about PBDE metabolism in humans and rodents. Several studies of human serum (15,16) and rat plasma (17) have reported that OH-PBDEs are important metabolites of PBDEs. In this study, fewer OH-PBDEs than expected were found in cat serum, considering the high body burden of native PBDEs. In addition, it is likely that the most prominent PBDE found in the cats of this study (i.e., 6-OH-BDE47) was of natural origin; the source of this metabolite is unclear but may be ingested by the cat through contamination in its food.

The Bottom Line

Overall, it is clear that cats are heavily exposed to PBDEs, mainly via indoor dust and food. Textiles, furniture, carpets and electronic equipment are important sources for exposure of PBDEs in indoor air. Cats would be expected to have a higher exposure to PBDE than humans due to intake of dust-bound PBDEs from their behavior e.g. walking close to the floor, collecting dust in their fur, and then ingesting these dust-enriched chemicals because of the their natural cleaning behavior.

It is also notable how poorly PBDE hydroxyl metabolites are formed by cats. Far lower concentrations are observed in their serum than expected based on their PBDE exposures. Accordingly, it is clear that cats have poor ability to metabolize PBDEs to OH-PBDEs, which is much different that man or rats.

Brominated flame retardants, as well as a number of other common environmental contaminants present in cat food and in the indoor environment, have been found to disturb the thyroid homeostasis, but the mechanisms and the extent of exposure necessary to obtain such disturbance in cats is not clear.  It is also possible that other nutritional factors or environmental pollutants could interact to have an additive or synergistic effect with this high PBDE exposure, which could contribute to the development of feline hyperthyroidism (3).

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  3. Peterson M. Hyperthyroidism in cats: What's causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818. 
  4. Dye JA, Venier M, Zhu L, et al. Elevated PBDE levels in pet cats: sentinels for humans? Environ Sci Technol 2007;41:6350-6356. 
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  7. Johnson PI, Stapleton HM, Mukherjee B, et al. Associations between brominated flame retardants in house dust and hormone levels in men. Sci Total Environ 2013;445-446:177-184.  
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  10. Norrgran J, Athanassiadis I, Jones B, et al. Are serum levels of brominated flame retardants and thyroid status correlated in cats? Organohalogen Compd 2012.
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  12. Norrgran J, Jones B, Lindquist NG, et al. Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism. Arch Environ Contam Toxicol 2012;63:161-168. 
  13. Hites RA. Polybrominated diphenyl ethers in the environment and in people: A meta-analysis of concentrations. Environ Sci Technol 2004;38: 945–56. 
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  15. Athanasiadou M, Cuadra SN, Marsh G, et al. Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua. Environ Health Perspect 2008;116:400-408. 
  16. Qiu X, Bigsby RM, Hites RA. Hydroxylated metabolites of polybrominated diphenyl ethers in human blood samples from the United States. Environ Health Perspect 2009;117:93-98.
  17. Malmberg T, Hoogstraate J, Bergman A, et al. Pharmacokinetics of two major hydroxylated polychlorinated biphenyl metabolites with specific retention in rat blood. Xenobiotica 2004;34:581-589. 

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