Interactive effects of developmental PCB exposure and relevant environmental risks on the auditory system

Polychlorinated biphenyls (PCBs) are environmental contaminants that can cross the mammalian placenta and mobilize from fat stores into breast milk to affect the developing offspring. Developmental PCB exposure has been shown to cause auditory deficits that last through adulthood. We assessed the interaction of PCBs with other environmental risks to examine if there were additive or interactive effects on auditory function. Rats were exposed developmentally to a unique environmental PCB mixture, the Fox River PCB mixture (FRM), and/or to molar equivalent doses of a commercial polybrominated diphenyl ether (PBDE) mixture, DE-71, that represents the PBDEs found in humans to assess the potential for additive effects of PCBs and PBDEs on cochlear function. In adulthood, the cochlear integrity of the offspring was tested by measuring distortion product otoacoustic emissions (DPOAEs). DPOAE amplitudes were decreased and thresholds were elevated in the 6 mg/kg PCB group. Exposure to PBDEs alone did not cause DPOAE deficits. Importantly, there was an interactive effect from combined exposure such that the individual low doses of PCBs and PBDEs did not result in DPOAE deficits, but the two combined produced a deficit similar to that of the high dose PCB group. These effects were accompanied by sharp reductions in thyroxine (T4) concentrations measured in littermates at weaning. We then assessed the interaction of developmental PCB exposure and noise exposure during adulthood to evaluate whether early PCB exposure increased the susceptibility to noise-induced hearing loss (NIHL). Since PCBs are known to cause hearing deficits via outer hair cell (OHC) damage, and the OHCs protect the inner ear from noise-induced damage, it was hypothesized that PCB-exposed rats would have more severe NIHL after intense noise exposure. Half of the rats developmentally exposed to PCBs were exposed to 97dB octave-band noise centered at 8 kHz for 4 hours a day for 5 consecutive days. Baseline DPOAEs were decreased in the PCB groups with the clearest effect in the 6 mg/kg PCB group. Rats in the 0, 1 and 3 mg/kg PCB groups all showed the same amount of temporary hearing loss 1 day after noise exposure, with partial recovery by 28 days after noise exposure. The PCB-exposed groups did not show any evidence of an increased susceptibility to the noise. Surprisingly, many of the rats in the 6 mg/kg PCB group exhibited behavior characteristic of the first stage of audiogenic seizures (AGS), known as wild running near the onset of noise exposure and had to be excluded from this study. This led to a study to examine whether developmental PCB exposure increases the susceptibility to AGS in adulthood. Once rats completed the NIHL study, they were subjected to loud noise for 2 min, starting at 100dB, and they were re-exposed after 24-48 to hours at 105dB and then at 110dB if they did not exhibit clonus seizures at the lower noise intensities. Female rats exposed to 3 or 6 mg/kg PCBs had significantly higher incidences of AGS compared to controls. Male rats exposed to 6 mg/kg PCBs had higher incidences of AGS compared to noise-naïve (NN) controls, but not compared to controls used in the earlier NIHL study. These effects were accompanied by sharp reductions in T4 concentrations measured at weaning in the PCB animals. These series of studies not only confirmed that developmental PCB exposure causes long term deficits in the auditory system that are still present in adulthood, but also demonstrated that PCBs can interact with other environmental risks to worsen the effects seen with PCBs alone.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Poon, Emily

Contributors dc:contributor

• Schantz, Susan L.
• Juraska, Janice M.
• Raetzman, Lori T.
• Wickesberg, Robert E.

• Polychlorinated biphenyl (PCB)
• polybrominated diphenyl ether (PBDE)
• distortion product otoacoustic emission (DPOAE)
• Audiogenic Seizures

Statement dc:rights

• Copyright 2012 Emily Poon

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/34355

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/34355