Hearing loss following exposure during development to polychlorinated biphenyls: a cochlear site of action.
Maternal exposure to polyhalogenated hydrocarbons results in early postnatal hypothyroxenemia and a low-frequency hearing loss in adult offspring (Goldey et al., 1995a. Toxicol. Appl. Pharmacol. 135, 67-76; Herr et al., 1996. Fundam. Appl. Toxicol. 33, 120-128). The purpose of the present work was to determine whether the site-of-action of this auditory impairment was within the cochlea. Primiparous Long-Evans rats were given daily oral doses of corn oil (control) or 8 mg/kg of the commercial PCB mixture Aroclor 1254 (A1254) from gestation day (GD) 6 through postnatal day (PND) 21. Auditory thresholds for 1-, 4-, 16-, and 40-kHz tones were assessed using reflex modification audiometry in young adult offspring on postnatal days (PND) 92-110. Approximately 6 weeks after auditory assessments, a subset of animals (n=4 per group) were killed for histological assessment of the cochlea. Surface preparations of the organ of Corti were prepared from one cochlea per animal and modiolar sections were prepared from the opposite cochlea. Consistent with previous findings, auditory thresholds for 1-kHz tones were elevated by approximately 25 dB in the A1254-exposed animals. Thresholds for all higher frequencies were not different compared to controls. Surface preparations of the organ of Corti revealed a mild to moderate loss of outer hair cells in the upper-middle and apical turns. Inner hair cells were not affected. Modiolar sections failed to reveal alterations in any other cochlear structures. There was also no apparent loss of ganglion cells. These data clearly link the loss of low-frequency hearing caused by exposure during development to A1254 to a loss of outer hair cells in the organ of Corti. The mechanism that underlies this developmental ototoxicity remains to be determined. These data provide the first evidence of a structural deficit in the nervous system of adult animals exposed to PCBs during development.
Crofton
K M
KM
Neurotoxicology Division, MD-74B, National Health and Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC 27711, USA. crofton.kevin@epa.gov
Ding
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D
Padich
R
R
Taylor
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M
Henderson
D
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D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects; D003638:Deafness / Q000139:chemically induced*; D004785:Environmental Pollutants / Q000506:poisoning*; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D008297:Male; D011078:Polychlorinated Biphenyls / Q000506:poisoning*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls