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HYDRONEPHROSIS IN MICE EXPOSED TO TCDD-CONTAMINATED BREAST MILK: IDENTIFICATION OF THE PEAK PERIOD OF SENSITIVITY AND ASSESSMENT OF POTENTIAL RECOVERY
Citation:
Couture, L. AND e. al. HYDRONEPHROSIS IN MICE EXPOSED TO TCDD-CONTAMINATED BREAST MILK: IDENTIFICATION OF THE PEAK PERIOD OF SENSITIVITY AND ASSESSMENT OF POTENTIAL RECOVERY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/121 (NTIS PB91211441).
Description:
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of hydronephrosis in mice both pre- and post-natally. ritical period of sensitivity to TCDD could not be identified for the hydronephrotic response induced prenatally since the urinary tract appeared equally sensitive throughout organogenesis. o identify the critical period of susceptibility for development of TCDD-induced hydronephrosis in neonatal mice, as well as to characterize the potential for recovery from this renal lesion, dose-response and time-course studies were conducted using lactational exposure. regnant C57BL/6N mice were allowed natural delivery. n the dose-response phase of this investigation, mothers were dministered 0, 3, 6, or 12 ug TCDD/kg once by gavage on post natal day (pnd) 1, 4, 8, or 14, and dams and pups were sacrificed on pnd 26. n the time-course studies, dams were given a single oral dose of 0 or 9 ug TCDD/kg on pnd 1, and mothers and litters were subsequently sacrificed on pnd 7, 13, 19, or 26. eonatal kidneys were examined, and hydronephrotic severity was scored. he incidence and severity of hydronephrosis were significantly elevated above controls at all dose levels on pnd 26 following treatment on pnds 1 and 4, while treatment on pnd 8 or 14 was ineffective at inducing hydronephrosis. n 26 day old pups, the incidence and severity of the renal lesion were significantly greater following treatment on pnd 1 than on all other exposure days. oth hydronephrotic incidence and severity increased with time to sacrifice following treatment on pnd 1. hus, recovery does not appear to occur between pnds 7-26 with the dosing regimen used In this study. ex-related differences were observed, as the hydronephrotic response in males was generally greater than in females. n conclusion, pnd 1 is the peak postnatal period of sensitivity to TCDD, as measured by the hydronephrotic response.
