Toxic legacy: Fish pass flame retardants, impaired health to offspring

A new study has found that fish exposed to low levels of common flame retardants called PBDEs for most of their lives pass the chemicals – and more surprisingly, the associated toxic effects – along to their progeny. While parents’ health effects were minimal, the exposures reduced hatch rates and altered the thyroid hormone system of the next generation. Effects were worse if the offspring were also exposed to the same low chemical levels as their parents, a situation that would mimic wild fish in a natural environment. The findings – published in the journal Environmental Science and Technology – broadly suggest that the toxic effects of PBDE exposure may magnify in subsequent generations of wild fish. The new findings are important because they show that flame retardants can trigger thyroid hormone disruption in the next generation whether or not the offspring are exposed to the chemicals. Polybrominated diphenyl ethers (PBDEs) are chemical flame retardants widely used in the United States. Manufacturers add PBDEs to furniture, foam cushions, mattresses, electronics, clothing and many other products to slow the spread of flames if they catch fire. Flame retardants are found in more than 80 percent of cushions used in car seats, portable cribs and other baby products (Stapleton et al. 2011). Human exposure to flame retardants occurs when people breathe contaminated air and dust or eat contaminated food (Schecter et al. 2010). Exposure to the chemicals is nearly universal; 97 percent of U.S. adults included in the nationally representative National Health and Nutrition Examination Survey had detectable PBDE levels in their blood (Sjödin et al. 2008). According to a 2009 report by the U.S. National Atmospheric and Oceanic Administration, PBDEs are also ubiquitous in coastal environments where they pose a risk to aquatic wildlife and human health. PBDEs may trigger toxic outcomes by disrupting the developing thyroid hormone system. The thyroid gland – a major player in the endocrine system – produces thyroid hormones called T3 and T4. These thyroid hormones work to regulate metabolism, growth and development. Chemicals that are structurally similar to thyroid hormones – like PBDEs – are thought to disrupt thyroid hormone signalling and adversely impact processes that depend on the hormones. PBDEs can be transferred through the mother to the next generation. This transfer is documented in fish, frogs, birds, rats and people. Because PBDEs affect the thyroid and thyroid hormones are critical to development, the chemicals are believed to impact offspring’s health. For example, high levels of PBDEs in mothers have also been associated with low birth weights in babies (Harley et al. 2011), increased difficulty becoming pregnant, and elevated thyroid hormone signalling during pregnancy (Harley et al. 2010). Due to unique and strict flammability standards in California, the United States and Canada account for the vast majority of the world market for commercial mixtures of brominated flame retardants. Their pervasive use and potential risk to human health raise questions about the widespread use of the chemicals and the role that lobbyists play in creating and supporting legislation that requires their use. During the new study, the researchers from the City University of Hong Kong continuously exposed zebrafish to three different levels of a commercial flame retardant mixture – called DE-71 – for five months from egg fertilisation to adulthood. The three concentrations – 1, 3 and 10 micrograms per litre (?g/L) – mimic levels found in the environment. They then measured flame retardant levels in the adult fish. To look for signs of endocrine disruption, they also measured levels of the thyroid hormones T3 and T4 in the blood of the adult fish. Pairs of some of the adults were moved to clean water and bred. The fertilised eggs were collected and divided into two groups. In one group – the unexposed group – the offspring were raised in clean water. The researchers measured the flame retardants transferred from the parents and the levels of T3 and T4 in the embryos and hatched larvae. The eggs in the other group were exposed to the same three concentrations of DE-71 as their parents. The two groups were compared to determine if the exposed offspring were more susceptible to the flame retardants than offspring raised in the clean water and exposed only to chemicals transferred from the parents. Researchers determined the survival and growth rate in the parents and the hatching, birth defect, survival and growth rates in the unexposed and exposed offspring. They also evaluated gene expression changes in the brain and liver in the parents and the unexposed and exposed offspring. The researchers discovered that the fish exposed to low levels of the flame retardants for their entire life developed normally. While the fish did accumulate different types of brominated flame retardants in their tissues, they did not exhibit overt signs of toxicity. However, increased levels of T4 were observed in females treated at the highest dose. The offspring had a different and more complicated story. The flame retardants were present in the eggs, indicating that the chemicals were transferred to them from the exposed adults. As expected, the higher the exposure level, the greater the levels of flame retardants in the eggs. Elevated levels of T3 and T4 – markers of thyroid endocrine disruption – were also seen in the eggs and the hatched fish whose parents were exposed to the 3 and 10 µg/L of the flame retardant mixture. Furthermore, at the two highest exposure levels, fewer fish hatched and those that did weighed less than offspring of unexposed fish. The offspring – the larvae and the embryos – were more susceptible if they too were exposed to the flame retardants. Researchers observed physical birth defects in the offspring that were exposed to the flame retardants at 3 or 10 µg/L when compared to the young that grew up in clean water. They were also more sensitive to the effects of the flame retardants on hatching rates and body weight. For the first time, researchers saw adverse effects – reduced hatching and body weights – in fish exposed to 1 µg/L of the flame retardant mixture. Higher levels of T4 were measured in the 10-day-old fish exposed to the highest concentration of the flame retardant mixture. The initial parental exposures altered gene expression in the offspring. The affected genes are involved in thyroid gland development and thyroid hormone synthesis and transport. Flame retardants directly handed down from an exposed parent to its offspring can skew the progeny’s early development and increase thyroid hormone levels, finds this study with zebrafish. And the effects got worse in the next generation if they, too, were exposed to the same contaminants. The long-term, low-level exposures used in the study offer a good way to assess multigenerational health risks because they represent levels in the environment that wild fish would encounter. The results are important because they show that flame retardants trigger thyroid hormone disruption not only in the exposed parent but also in subsequent generations. As the eggs hatched and the embryos developed, they did not grow as fast and weighed less than fish whose parents were not exposed. These growth changes were associated with thyroid hormone disruptions triggered by the PBDEs. Development was more strongly impaired in the youngsters that were also living in contaminated water. The study is unique because it suggests the growing offspring were more sensitive to PBDEs than their parents. The results imply that wild fish that live in the same environment as their parents may experience increased toxicity that could magnify over subsequent generations. Exactly how the flame retardants influence the second generation’s thyroid hormone system is not well understood. At least two avenues appear important: parents – especially the mothers – can deposit more than normal levels of thyroid hormones directly in the eggs, and/or the flame retardants passed along from the parents may themselves influence hormone levels in the developing fish.

Environmental Health News, 11 January 2012 ; ;