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.
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 polychlorinated biphenyl (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 PND 130. 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 PND 168-175. 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 PND 300-310 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 the serotonergic systems, 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.
Toxicology Group, Wageningen University and Research Center, 6703 HE Wageningen, The Netherlands. ilonka.meerts@notox.nl
Ilonka A T M
IA
Meerts
Hellmuth
H
Lilienthal
Saske
S
Hoving
Johannes H J
JH
van den Berg
Bert M
BM
Weijers
Ake
A
Bergman
Jan H
JH
Koeman
Abraham
A
Brouwer
D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D038081:Organogenesis / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013963:Thyroid Hormones / Q000097:blood
C111120:2,3,3',4',5-pentachloro-4-hydroxybiphenyl; D018377:Neurotransmitter Agents; D013963:Thyroid Hormones; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls