Brominated diphenyl ether (BDE) levels in liver, adipose, and milk from adult and juvenile rats exposed by gavage to the DE‐71 technical mixture

Abstract

Brominated diphenyl ethers (BDEs) are used as flame retardants in consumer products. Rodent studies indicate that the liver, thyroid, and nervous system of developing animals are targets of BDEs. To explore the relationship between exposure and health in developing animals, BDE accumulation in adult and juvenile rats was examined in conjunction with changes in liver weight and serum thyroxine (T4). Adult (F0) rats received the commercial BDE mixture DE-71 by gavage at doses of 0.5, 5, and 25 mg kg(-1) body weight (bw)/day for 21 weeks. F0 rats were mated and exposure continued throughout breeding, pregnancy, lactation, and postweaning until the pups (F1 generation) reached postnatal day (PND) 42. Milk was collected from lactating dams. Adipose and liver samples were collected from F0 and F1 males and females for BDE congener analysis. Congener prevalence in rat tissues mimicked congener prevalence in wildlife and humans. Tissue concentrations of all congeners except BDE-153 were lower than would be expected based on dose proportionality, confirming that BDE-153 has a high capacity for bioaccumulation. BDEs were transferred from maternal tissues to milk during lactation. Milk congener profiles differed from maternal tissue profiles indicating that degree of bromination and maternal sequestration influenced BDE transfer to milk. Female F1 rats accumulated more BDEs than F1 males, indicating that female rats were less able to metabolize and/or excrete BDEs. Significant effects on liver weight and serum T4 levels were observed in adults and juveniles in the middle and high dose groups, corresponding to BDE levels in the μg g(-1) range. Although it remains to be determined how human liver and thyroid are affected by exposure to much lower BDE levels, the present study confirmed that gender and reproductive status influence BDE accumulation in tissues and BDE transfer to the neonate via milk.

Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression

“…Both serum T3 and T4 concentrations were markedly increased in the F1 mothers on Day 14.5 of pregnancy and thyroid gland weight was markedly elevated at five months of age in the F1 females. By contrast, there are developmental, 25–27 peripubertal 21,27,28 and adult 29,30 studies in rodents employing much higher doses of DE-71 or its congeners than we used that report PBDEs to decrease serum T4 concentrations 25–27,29,30 or serum T3 and T4 concentrations. 21,28 When liver weights were measured, these effects were associated with PBDE regimens that increased liver weights.…”

“…21,28 When liver weights were measured, these effects were associated with PBDE regimens that increased liver weights. 21,25–27 PBDEs share structural similarity to thyroid hormones (Figure 1). High levels of PDBEs have been shown to alter thyroid hormone levels and clearance and can compete for thyroid hormone serum binding protein transthyretin.…”

In Utero and Childhood Polybrominated Diphenyl Ether Exposures and Body Mass at Age 7 Years: The CHAMACOS Study

“…Serum PBDE concentration is determined by the amount and route of exposure, homeostasis between tissues and extracellular fluids, and rates of metabolism and excretion ( Staskal et al 2006 ). Because each PBDE congener has different absorption rates from the gastrointestinal tract, lipophilicity, adipose tissue/serum concentration ratios, and elimination rates, individual serum congener measurements may not always reflect the level of external exposure or total body congener amount, and therefore may not be comparable ( Bondy et al 2011 , 2013 ; Sanders et al 2006 ; Staskal et al 2006 ). For example, in our study population, the prevalence of obesity increased with age.…”

“…As suggested previously for PBDEs and for other lipophilic compounds ( Chevrier 2013 ), this weight gain might create an additional adipose tissue reservoir for storage of PBDEs, leading to diluted, and thus lower, concentrations in heavier individuals ( Glynn et al 2003 ). Thus, reverse causality may explain the inverse association of children’s serum BDE-153 concentration with children’s BMI z -score, waist circumference z -score, and overweight/obesity status, especially because BDE-153 is the most lipophilic, has the highest bioaccumulation capacity and adipose tissue/serum concentration ratio, and the lowest rate of metabolism and excretion ( Bondy et al 2011 ; Sanders et al 2006 ; Staskal et al 2006 ) compared with the other PBDEs measured. A cross-sectional study in adults that reported a negative association only between serum BDE-153 levels and BMI provides additional support ( Lim et al 2008 ).…”

Polybrominated Diphenyl Ethers (PBDEs) in Aborted Human Fetuses and Placental Transfer during the First Trimester of Pregnancy

“…Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants and have become ubiquitous pollutants in the environment. − Because of their potential to bioaccumulate, PBDEs have been found in various biotic samples worldwide. , High PBDE concentrations have also been reported in human tissues, such as blood, adipose tissue, placenta, and semen. − There is an increasing amount of data showing that PBDEs have a range of adverse effects, including thyroid hormone disruption, permanent learning and memory impairment, behavioral changes, hearing deficits, delayed puberty onset, decreased sperm count, and fetal malformations in laboratory animals. − It is believed that exposure to PBDEs in utero or during infancy could lead to more significant harm than exposure during adulthood and at much lower concentrations. − …”