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ToxSci Advance Access published online on August 13, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh252
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received May 31, 2004
Accepted August 6, 2004

Neurotoxicology

Developmental Exposure to 4-Hydroxy-2,3,3',4',5-Pentachlorobiphenyl (4-OH-CB107): Long Term Effects on Brain Development, Behavior and Brain Stem Auditory Evoked Potentials in Rats

Ilonka A. T. M. Meerts 1*, Hellmuth Lilienthal 2, Saske Hoving 1, Johannes H. J. van den Berg 1, Bert M. Weijers 3, Åke Bergman 4, Jan H. Koeman 1, Abraham Brouwer 5

1 Toxicology Group, Wageningen University and Research Center, Tuinlaan 5, 6703 HE, Wageningen, The Netherlands
2 Medical Institute of Environmental Hygiene, Department of Neurobehavioral Toxicology, Düsseldorf, Germany
3 Laboratory Animal Center, Wageningen University and Research Center, Wageningen, The Netherlands
4 Department of Environmental Chemistry, Wallenberg Laboratory, Stockholm University, Stockholm, Sweden
5 Toxicology Group, Wageningen University and Research Center, Tuinlaan 5, 6703 HE, Wageningen, The Netherlands; Institute for Environmental Studies, Vrije Universiteit of Amsterdam, Amsterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: ilonka.meerts{at}notox.nl.


  Abstract

In the present study the developmental neurotoxic effects of the PCB metabolite 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) were compared with effects caused by a mixture of parent PCB congeners (Aroclor 1254). Pregnant female Wistar rats were exposed to 0.5 or 5 mg 4-OH-CB107, or 25 mg Aroclor 1254 per kg body weight from gestation days 10 to 16. Plasma thyroid hormone levels were significantly decreased in the offspring of all treatment groups at postnatal day 4 (PND 4). Behavioral experiments using an open field paradigm revealed an impaired habituation in male offspring of all treatment groups at PND130. Passive avoidance experiments indicated significant influences on the time course of step-down latencies across trials in exposed male rats. Catalepsy induced by haloperidol showed increases in latencies to movement onset in female offspring exposed to 0.5 mg 4-OH-CB107 compared to Aroclor 1254 treated offspring at PND168-175. Male offspring exposed to 4-OH-CB107 or Aroclor 1254 showed decreases in latencies compared to control animals. Brain stem auditory evoked potentials (BAEPs) measured at PND300-310 showed significant increases in auditory thresholds in the low frequency range between Aroclor 1254 and 4-OH-CB107 (5 mg/kg bw) treated animals. Measurements of neurotransmitter levels revealed effects of Aroclor 154 exposure on both the dopaminergic and serotonergic system, whereas 4-OH-CB107 exposure affected dopaminergic and noradrenergic systems, with slight but not significant effects on the serotonergic system.

These results indicate that 4-OH-CB107 is able to induce long-term effects on behavior and neurodevelopment. The observed effects for 4-OH-CB107 are similar to, but in some aspects different from the effects observed after Aroclor 1254 exposure.


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