Porphyrogenic effect of pentabromodiphenyl ether after repeated administration to rats

Abstract

Until recently, pentabromodiphenyl ether (PentaBDE) was most commonly used as a flame retardant. On account of the hazardous effect of PentaBDE on the environment, its use was discontinued some years ago. The toxicity of this compound has been well documented in the literature, especially with regard to the endocrine system, induction of liver microsomal enzymes, and disturbance of redox homeostasis. The aim of this study was to investigate the porphyrogenic effect of PentaBDE after its repeated administration to rats at doses of 2, 8, 40, or 200mg/kg/day. After a 28-day exposure, a dose-dependent increase (maximum 2.5-fold) in ALA-S activity in the liver was observed. The enhanced concentration of total porphyrins in the liver (3- to 19-fold after doses of 8-200mg/kg/day) was also found. The most pronounced changes in liver concentrations of porphyrins were shown by high carboxylated porphyrins (a 19-fold increase for octacarboxyporphyrins and a 36-fold increase for heptacarboxyporphyrins). They made over 95% of total porphyrins accumulated in the liver. The porphyrogenic effect of PentaBDE was also evidenced by the augmented urinary excretion of total porphyrins. After 28days of exposure, the observed changes (2- to 7-fold increase) were found to be dose-dependent. Tetracarboxyporphyrins predominated in urine; their urinary concentrations were 4-12 times higher, and their daily urinary excretion is 2-9 times higher. A dose of 2mg/kg/day was the lowest dose that caused changes in the levels of porphyrins (LOAEL). The experiment revealed the effect of PentaBDE on the heme biosynthesis and porphyrin concentrations, which indicates its porphyrogenic effect.