title: Octabromodiphenyl ether - porphyrogenicity after repeated administration to rats.
abstract: OBJECTIVE
  Octabromodiphenyl ether (OctaBDE) is a flame retardant which has been withdrawn from common use due to its negative effect on the environment. The literature data regarding its toxicity addresses its effect on liver function, the endocrine and reproductive systems, as well as its developmental toxicology aspects. The aim of this study was to investigate the effect of repeated administration of OctaBDE on heme biosynthesis in rats.
  
  
  METHODS
  The study was performed on female Wistar rats. OctaBDE was administered intragastrically at four different doses (2, 8, 40 or 200 mg/kg/day) for 7, 14, 21 or 28 days. The following measures of heme synthesis disturbance were used: urinary excretion of porphyrins, liver concentration of porphyrins, the activity of delta-aminolevulinate synthase (ALA-S) and delta-aminolevulinate dehydratase (ALA-D) in the liver.
  
  
  RESULTS
  After 28 days of exposure, lower ALA-S and ALA-D activity was observed in the liver. Additionally, increased concentrations of high carboxylated porphyrins (octa- and heptacarboxyporphyrins) were found in the liver: from 2- to 10-fold after the 2 mg/kg/day doses and from 4- to 14-fold after the 8-200 mg/kg/day doses. The porphyrogenic effect of OctaBDE was also evidenced by augmented, dose-dependent and exposure time-dependent, concentrations of total porphyrins in urine (2-7.5-fold increase) and their urinary excretion (2-9-fold increase). Tetracarboxyporphyrins predominated in the urine; their concentrations increased 2.5-10 fold.
  
  
  CONCLUSIONS
  The study revealed that repeated exposure to OctaBDE affects heme biosynthesis and the levels of porphyrins. The lowest effective level which induced changes in porphyrin concentration was 2 mg/kg/day.
authors.affiliation: Department of Toxicology, Medical University of Łódź, Łódź, Poland. elzbieta.bruchajzer@umed.lodz.pl
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Bruchajzer
authors.forename: Barbara
authors.initials: B
authors.lastname: Frydrych
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Szymańska
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005411:Flame Retardants / Q000494:pharmacology / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006418:Heme / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced*; D011166:Porphyrins / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D011166:Porphyrins; D006418:Heme; D000624:5-Aminolevulinate Synthetase