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Flame Retardants

Flame retardants and diabetes/obesity
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Flame retardants are chemicals added to furniture and electronics. Brominated flame retardants (BFRs) include compounds such as polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), and hexabromocyclododecane (HBCD). PBDEs are present in consumer products such as furniture and electronics, and exposure is largely through house dust. PBDEs have been banned or are being phased out throughout much of Europe and North America. One substitute is Firemaster 550, added to furniture foams and children's products, also found in house dust. HBCD is used in textiles and polystyrene foam, such as in automobile interiors. PBBs were banned in the U.S. in the 1970s, and current exposure is largely through diet. In general, flame retardant chemicals can accumulate in body tissues.

Type 2 Diabetes, Metabolic Syndrome, and Body Weight

Longitudinal Studies in Humans

The strongest evidence for the ability for environmental exposures to contribute to the development of diabetes comes from longitudinal studies. These are studies that take place over a period of time, where the exposure is measured before the disease develops.
A long-term study from Michigan found that levels of PBBs were not associated with diabetes risk. The people in this study were exposed to very high levels of PBBs for about eight months during the 1970s (Vasiliu et al. 2006).

Exposure During Development

Evidence is growing that exposure to pollution during critical developmental periods, such as in utero or during childhood, may have effects later in life. A long-term study from California found that mothers' PBDE levels during pregnancy were associated with a higher body mass index (BMI) in their sons, but a lower BMI in their daughters at age 7. Also, the child's PBDE levels were associated with a lower BMI at age 7 (Erkin-Cakmak et al. 2015).

A study from Cincinnati, Ohio, found that prenatal PBDE levels generally were not associated with height or weight in children, although a few were associated with lower weight-related measures in childhood (Vuong et al. 2016). 

A long-term Spanish study of 27 different endocrine disrupting chemicals found that in utero levels of various persistent organic pollutants were associated with overweight/higher BMI at age 7, while other chemical levels (flame retardants, arsenic, BPA, phthalates, lead, and cadmium) were not associated (Agay-Shay et al. 2015).

A study from North Carolina found that PBDE levels in breastmilk were not associated overall with growth in children through age 3. However in boys, PBDE levels were associated with a lower weight-to-height ration, while in girls they were associated with higher weight-to-height (with the exception of BDE-153, which showed the opposite association) (Hoffman et al. 2016).

PBDE exposures in the mother have been associated with lower birthweight of the baby (Chao et al. 2007 Harley et al. 2011; Lignell et al. 2013), and with epigenetic changes related to fetal growth (Zhao et al. 2016).

Cross-Sectional Studies in Humans

Cross-sectional studies are studies that measure exposure and disease at one point in time. These provide weaker evidence than longitudinal studies, since the disease may potentially affect the exposure, and not vice versa.

Lim et al. (2008) studied exposure to BFRs using the U.S. National Health and Nutrition Examimation Survey (NHANES) dataset, a U.S.-wide survey of chemical exposures, nutrition, and health conditions. They found that two of six flame retardants (PBB-153 and PBDE-153) were associated with both diabetes and metabolic syndrome (a cluster of conditions that are common in people with diabetes). The two chemicals had different dose response curves. PBB-153 was positively associated with diabetes, in that the risk increased as the levels of exposure increased. PBDE-153 was also associated with diabetes, but in the highest exposure group, the trend decreased slightly. Similar trends were seen in the associations with metabolic syndrome: steadily increasing for PBB-153, and increasing then decreasing for PBDE-153. These unusual dose-response relationships have been seen in animal studies of endocrine disrupting compounds. It may be that the effects of PBBs show up at lower doses, and at higher exposure levels, the risk would level off or even decrease (Lim et al. 2008).

In a study from Finland, where PBDE levels are lower, researchers found that PBDE-47 and PBDE-153 were not associated with type 2 diabetes in elderly adults (Airaksinen et al. 2011).

In China, PBDE-47 were associated with diabetes in two independent community-based studies (Zhang et al. 2016).

Laboratory Studies

The study from China mentioned above also found that rats exposed to PBDE-47 for 8 weeks developed high blood glucose levels (Zhang et al. 2016). Another study also found that male rats exposed to various flame retardants developed high glucose levels, plus had other metabolic effects that varied by chemical and sex of the rat (Krumm et al. 2017). 

Mice exposed to HBCD gained more weight and had higher blood sugar and insulin levels (similar to type 2 diabetes) than unexposed mice. These effects were strongest in the mice fed a high-fat diet, as opposed to a normal diet (Yanagisawa et al. 2014). For an article describing this study, see Flame retardant linked to obesity in mice, published by Environmental Health News.

Low doses of BDE-47, the PBDE that is most abundant in human tissues, was given to female mice while pregnant and lactating. Pups had increased body weight and body length during the first few months of life. Exposure also increased glucose uptake in male pups (Suvorov et al. 2009).

Chronic exposure to the PBDE known as penta-BDE disturbs glucose and insulin metabolism in fatty tissue of rats, characteristics associated with type 2 diabetes, insulin resistance, and obesity (Hoppe and Carey 2007). DE-71, a mixture of PBDEs, also disturbs whole-body glucose and insulin metabolism in rats, and may influence whole-body insulin resistance levels (Nash et al. 2013).

A rat study shows that PBDEs alters fat metabolism in the liver and increases blood ketone levels (Cowens et al. 2015).

Zebrafish exposed to natural mixtures of PBDEs and other persistent organic pollutants from Norwegian lakes showed increased body weight, as well as changes in the regulation of a variety of genes associated with body weight and insulin signalling (Lyche et al. 2010; Lyche et al. 2011).

Another type of flame retardant, triphenyl phosphate (TPhP), causes changes in glucose levels, and carbohydrate and lipid metabolism in zebrafish, an animal used to test chemical exposure effects (Du et al. 2016). 

How are we exposed?

Furniture label

Furniture labels that state that the item meets California's flammability requirement technical bulletin 117 likely contain high levels of chemical flame retardants.

Cell Culture Studies

Flame retardants can affect the insulin-producing beta cells in the pancreas. For example, BDE-47 and BDE-85 stimulate insulin secretion in beta cells (Karandrea et al. 2017).

The liver cells of fish exposed to various PBDEs and PBDE mixtures showed metabolic disturbances related to blood glucose control pathways (Søfteland et al. 2011). BDE-47 enhances the development of fat cells in cell culture studies (Kamstra et al. 2014).

According to a study of cell cultures, some compounds that are related to bisphenol-A (BPA) and used as flame retardants can activate PPARγ (peroxisome proliferator-activated gamma receptor), which play a role in glucose metabolism as well as fat storage Riu et al. 2011). For an article on this study, see Warm reception? Halogenated BPA flame retardants and PPARγ activation, published by Environmental Health Perspectives (Barrett 2011). The flame retardant tetrabromobisphenol A (TBBPA) damages pancreatic beta cells and induces beta cell death (Suh et al. 2017), as well as promotes fat cell development (Woeller et al. 2017). 

In fact, most types of tested flame retardants (including PBDEs, phthalates, and phenols) have been shown to activate PPARγ -- as does house dust, which is high in flame retardant chemicals (Fang et al. 2014).

Firemaster 550, a type of flame retardant mixture, also activates the PPARγ receptor, which may explain its potential to cause weight gain (as described in the following section) (Belcher et al. 2014). Firemaster 550 induces obesity in rodents. In human cells, it causes stem cells to turn into fat cells instead of bone cells (Pillai et al. 2014). For an article about this study, see More fat, less bone? Flame retardant may deliver a one-two punch, published in Environmental Health Perspectives (Nicole 2014). A further study found that Firemaster and two of its specific components can induce fat cell development in pre-fat cells (Tung et al. 2017).

Another flame retardant, triphenyl phosphate (which is also used in nail polish), as well as its metabolite, enhance the differentiation of fat cells and affect the glucose uptake of fat cells (Cano-Sancho et al. 2017).

Exposure During Development

Pregnant and lactating rats were exposed to the flame-retardant mixture Firemaster 550. The offspring developed signs of metabolic syndrome, including weight gain. Like other flame retardant chemicals, the chemicals used in Firemaster 550 accumulated in the body tissues of mothers as well as offspring, and had effects that suggested they disrupt the endocrine system (Patisaul et al. 2013). For an article describing this study, see Firemaster 550 identified as potential obesogen; linked to weight gain, early puberty, anxiety in rats, published in Environmental Health News The flame retardant triphenyl phosphate, a component of Firemaster 550 and also found in consumer products such as nail polish, causes increased body fat mass in rodents exposed during gestation until weaning. It also accelerates the development of diabetes in the males (Green et al. 2016).

A study of rats exposed to the flame retardant mixture DE-71 during development also were found to weigh more than unexposed controls (Bondy et al. 2013). And mice exposed to deca-BDE had lipid abnormalities in the mothers, inhibiting fetal growth and development (Chi et al. 2011). Another study, of zebrafish, also found that developmental exposure to these compounds promotes fat accumulation in larvae and weight gain in the juvenile fish (Riu et al. 2014).

The offspring of pregnant rats exposed to a mixture of flame retardants had higher cholesterol levels, although lower fat pad weight, and no change in glucose or insulin levels (Tung et al. 2017).

Four days after a single developmental exposure to the flame retardant HBCD, mice developed different metabolite levels that included metabolites involved in glycolysis, gluconeogenesis, and lipid metabolism (Szabo et al. 2016).

Exposure to flame retardants (BDE-47) in early life (but after weaning) led mice to develop insulin resistance-- but only if those mice were genetically susceptible (McIntyre et al. 2015).

Type 1 Diabetes

Could flame retardants affect the risk of type 1 diabetes? We don't know.

One animal study has found that treating adult male rats with the flame retardant BDE-209 for 8 weeks caused high blood sugar in those rats. A genetic analysis showed that BDE-209 induced changes in gene expression, including some that are involved in type 1 diabetes, and some involved in autoimmune thyroid disease (common in people with type 1 diabetes). The link to type 1 was supported by a decrease in insulin levels in the rats. They also found immune system changes similar to type 1, as well as inflammation and oxidative stress (Zhang et al. 2013).

Animal studies confirm that PBDEs affect the immune system (e.g., Lv et al. 2014; Zheng et al. 2014), including immune stimulation (Koike et al. 2013), during development (Liu et al. 2012), and at low levels of exposure (Fair et al. 2012). One study found that mice exposed to PBDEs had lower levels of the immune cells (cytokines) important in the defense of coxsackie virus (Lundgren et al. 2009). (Coxsackie virus is one of the viruses linked to type 1 diabetes; see the viruses page). These authors have also found that PBDEs affect the course of a virus in mice, and that the virus caused a higher accumulation of PBDEs in the liver (Lundgren et al. 2013).

There have been no human studies on type 1 diabetes and PBDEs, although I have met at least one person who found his child had high levels of PBDEs in blood after diagnosis with type 1. In Sweden, PBDEs were banned in the 1990s, and by the end of that decade, levels in Swedish women's breastmilk began to decline. (Overall, PBDE levels in the US are much higher than in Sweden). Curiously, Swedish children born beginning in the year 2000 show slightly lower risks of type 1 diabetes than those born earlier. (The incidence is still increasing in Swedish children, but not as rapidly). I wonder if these two trends could be related? (Howard 2011).

Gestational Diabetes

One study found that pre-conception levels of PBDE-153 (but not other chemicals) were indeed linked to an increased risk of developing gestational diabetes (Smarr et al. 2016). Another study, from Iran, found that total PBDE levels were associated with gestational diabetes as well (Eslami et al. 2016). A very small study of pregnant women in Shanghai, China, found that newer, organophosphate flame retardants were present in 100% of women, but were not associated with health effects, including gestational diabetes (Feng et al. 2016). I expect a larger sample size would be needed to show some associations.

The Bottom Line

Exposure to two types of brominated flame retardants are associated with type 2 diabetes and metabolic syndrome in people with low, background levels of exposure, although not in long-term studies. Animals exposed to flame retardants develop high blood sugar, gain weight, and show immune system effects and changes in gene expression linked to type 1 diabetes.

References

To download or see a list of all the references cited on this page, see the collection Flame retardants and diabetes/obesity in PubMed.