| Developmental Exposure to Low Dose PBDE 99: Effects on Male Fertility and Neurobehavior in Rat Offspring Sergio N. Kuriyama, Chris E. Talsness, Konstanze Grote, and Ibrahim Chahoud Institute of Clinical Pharmacology and Toxicology, Department of Toxicology,
Charité University Medical School Berlin,
Campus Benjamin Franklin, Berlin, Germany Abstract
In utero exposure to a single low dose of 2,2´,4,4´,5-pentabromodiphenyl ether (PBDE-99) disrupts neurobehavioral development and causes permanent effects on the rat male reproductive system apparent in adulthood. PBDEs, a class of flame retardants, are widely used in every sector of modern life to prevent fire. They are persistent in the environment, and increasing levels of PBDEs have been found in biota and human breast milk. In the present study we assessed the effects of developmental exposure to one of the most persistent PBDE congeners (PBDE-99) on juvenile basal motor activity levels and adult male reproductive health. Wistar rat dams were treated by gavage on gestation day 6 with a single low dose of 60 or 300 µg PBDE-99/kg body weight (bw) . In offspring, basal locomotor activity was evaluated on postnatal days 36 and 71, and reproductive performance was assessed in males at adulthood. The exposure to low-dose PBDE-99 during development caused hyperactivity in the offspring at both time points and permanently impaired spermatogenesis by the means of reduced sperm and spermatid counts. The doses used in this study (60 and 300 µg/kg bw) are relevant to human exposure levels, being approximately 6 and 29 times, respectively, higher than the highest level reported in human breast adipose tissue. This is the lowest dose of PBDE reported to date to have an in vivo toxic effect in rodents and supports the premise that low-dose studies should be encouraged for hazard identification of persistent environmental pollutants. Key words: development, endocrine active compounds, in utero exposure, low-dose effects, male fertility, neurobehavior, PBDE-99. Environ Health Perspect 113:149-154 (2005) . doi:10.1289/ehp.7421 available via http://dx.doi.org/ [Online 4 November 2004]
Address correspondence to I. Chahoud, Charité University Medical School Berlin, Campus Benjamin Franklin, Department of Toxicology, Garystrasse 5, 14195 Berlin, Germany. Telephone: 49-30-8445-1750. Fax: 49-30-8445-1761. E-mail: ibrahim.chahoud@charite.de We thank H. Marburger and B. Woelffel for exemplary technical assistance and C. Gericke for valuable support on statistical analysis and graphic layout. This work was supported by UBA-Forschungs- und Entwicklungsvorhaben grant 29965221/04. The authors declare they have no competing financial interests. Received 16 July 2004 ; accepted 4 November 2004.
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