title: Effects of the brominated flame retardant hexabromocyclododecane (HBCD) on dopamine-dependent behavior and brainstem auditory evoked potentials in a one-generation reproduction study in Wistar rats.
abstract: Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant which has been recently detected in many environmental matrices. Data from a subacute toxicity study indicated dose-related effects particularly on the pituitary thyroid-axis and retinoids in female rats. Brominated and chlorinated aromatic hydrocarbons are also reported to exert effects on the nervous system. Several investigations revealed a pronounced sensitivity of the dopaminergic system and auditory functions to polychlorinated biphenyls. Therefore, the present experiment should examine, whether or not HBCD affects these targets. Rats were exposed to 0, 0.1, 0.3, 1, 3, 10, 30 or 100 mg HBCD/kg body weight via the diet. Exposure started before mating and was continued during mating, gestation, lactation, and after weaning in offspring. Haloperidol-induced catalepsy and brainstem auditory evoked potentials (BAEPs) were used to assess dopamine-dependent behavior and hearing function in adult male and female offspring. On the catalepsy test, reduced latencies to movement onset were observed mainly in female offspring, indicating influences on dopamine-dependent behavior. The overall pattern of BAEP alterations, with increased thresholds and prolonged latencies of early waves, suggested a predominant cochlear effect. Effects were dose-dependent with lower bounds of benchmark doses (BMDL) between < or =1 and 10 mg/kg body weight for both catalepsy and BAEP thresholds. Tissue concentrations at the BMDL values obtained in this study were 3-4 orders of magnitude higher than current exposure levels in humans.
authors.affiliation: Neurotoxicology Group, BGFA - Research Institute for Occupational Medicine, German Social Accident Insurance, Ruhr University of Bochum, Buerkle de la Camp Platz 1, 44789 Bochum, Germany. lilien@bgfa.rub.de
authors.forename: Hellmuth
authors.initials: H
authors.lastname: Lilienthal
authors.forename: Leo T M
authors.initials: LT
authors.lastname: van der Ven
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.forename: Josephus G
authors.initials: JG
authors.lastname: Vos
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects*
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; C089796:hexabromocyclododecane; D004298:Dopamine