Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment

Abstract

Firemaster® 550 (FM 550), a fire-retardant mixture used in foam-based products, was recently identified as a common contaminant in household dust. The chemical structures of its principle components suggest they have endocrine disrupting activity, but nothing is known about their physiological effects at environmentally relevant exposure levels. The goal of this exploratory study was to evaluate accumulation, metabolism and endocrine disrupting effects of FM 550 in rats exposed to 100 or 1000 µg/day across gestation and lactation. FM 550 components accumulated in tissues of exposed dams and offspring and induced phenotypic hallmarks associated with metabolic syndrome in the offspring. Effects included increased serum thyroxine levels and reduced hepatic carboxylesterease activity in dams, and advanced female puberty, weight gain, male cardiac hypertrophy, and altered exploratory behaviors in offspring. Results of this study are the first to implicate FM 550 as an endocrine disruptor and an obesogen at environmentally relevant levels.

FIGURE 1

Chemical structures of the four FM 550 components.

FIGURE 2

Adipose levels of the FM 550 component TBB in dam (black bars) and pup (gray bars) adipose tissue on the day of weaning (PND 21). Samples were collected 60–330 min after exposure (n = 3/treatment; high dose = 1000 μg per day; low dose = 100 μg/day via oral administration to the dam across gestation and lactation).

FIGURE 3

Total thyroxine levels measured in dam serum collected on PND 21. Samples were collected 60–330 min after exposure (n = 3/treatment; bars depict means ± SEM; *p ≤ 0.05; high dose = 1000 μg per day; low dose = 100 μg/day via oral administration to the dam across gestation and lactation).

FIGURE 4

Hepatic carboxylesterase activity measured in dams on PND 21. Samples were collected 60–330 min after exposure (n = 3/treatment; bars depict means ± SEM. *p ≤ 0.05; high dose = 1000 μg per day; low dose = 100 μg/day via oral administration to the dam across gestation and lactation).

FIGURE 5

Offspring performance on the ZM (A, B) and EPM (C, D) differed by sex and exposure. As expected, performance among controls was sexually dimorphic, with females showing less anxiety than males, although latency to enter an open arm in the ZM did not reach statistical significance. FM 550 exposure was anxiogenic in both tests, an effect that was more pronounced at the higher dose. In males, effects were nonmonotonic in the ZM but inconclusive in the EPM because overall activity was so low (bar graphs depict means ± SEM; #p ≤ 0.05, ##p ≤ 0.01 compared to the opposite sex, *p ≤ 0.05, **p ≤ 0.01 compared to same sex controls (n = 11♂, 8♀); high dose = 1000 μg per day (n = 4♂, 5♀); low dose = 100 μg/day (n = 9♂, 11♀); via oral administration to the dam across gestation and lactation).

FIGURE 6

Female offspring in the high-dose (1000 μg/day; n = 4) group had significantly higher blood glucose levels 30 min after glucose administration (A) compared to unexposed controls (n = 6). No significant effect of low-dose exposure (100 μg/day; n = 9) was detected. A trend for an elevated AUC was detected in the high-dose group. (B) High-dose exposed females were significantly heavier than controls at the time of testing (C).

FIGURE 7

Impact of FM500 on LV wall thickness in the male offspring. The mean thickness of the LV wall was determined for controls (n = 9) and each exposure group. (A) Mean wall thickness for the control group was 2.58 mm (±0.06), 2.52 (±0.08), and 2.90 mm (±0.06) for low (100 μg; n = 9) and high (1000 μg; n = 4) dose groups, respectively. Shown in (B) are representative H&E stained heart sections from control and high-dose groups (RV = right ventricle; LV = left ventricle. Graphed values are ± SEM, * p ≤ 0.05 vs. controls).