PCBs, thyroid hormones, and ototoxicity in rats: Cross-fostering experiments demonstrate the impact of postnatal lactation exposure

Previous research has demonstrated the sensitivity of the developing rat to the hypothyroxinemic and ototoaic effects of perinatal exposure to Aroclor 1254 (A1254). We tested the hypothesis that postnatal exposure via lactati on is the major cause of the ototoxicity by cross fostering animals at birt h. Primiparous rats (22-24/dose) received 0 or 6 mg/kg A1254 (po in corn oi l) from gestation day (GD) 6 to postnatal day (PND) 21. On the day of birth , half of the treated litters and half of the control litters were cross-fo stered, resulting in the following groups: Ctrl/Ctrl (controls); A1254/A125 4 (perinatal exposure); A1254/Ctrl (prenatal exposure only); and Ctrl/A1254 (postnatal exposure only). We assessed offspring at a number of ages for: serum thyroid hormone concentrations, liver and brain concentrations of PCB s, body weight, mortality, age of eye opening, auditory startle amplitudes, and auditory thresholds for 1 kHz and 40 kHz tones. Circulating thyroxine (T-4) concentrations were sharply reduced at GD 21 in the A1254-exposed gro up, and on PND 3, 7, 14, and 21 in the A1254/A1254 and the Ctrl/A1254 group s. Smaller decreases in T-4 were observed in the A1254/Ctrl group on PND 3, 7, and 14. PCB concentrations in the liver on PND 21 were sharply elevated in the A1254/A1254 and Ctrl/A1254 groups. Much smaller increases were seen in the A1254/Ctrl group. Age of eye-opening and startle amplitudes were un affected by treatment. A1254 exposure caused permanent hearing deficits (20 dB increase) at the low frequency (1 kHz) in the A1254/A1254 and Ctrl/A125 4 groups. The present findings demonstrated that the critical period for th e ototoxicity of developmental A1254 exposure is within the first few postn atal weeks in the rat. This effect is consistent with the greater degree of postnatal hypothyroxinemia resulting from the greater magnitude of exposur e that occurs postnatally via lactation.