The sensitivity to 3,3'-iminodipropionitrile differs for high- and midfrequency hearing loss in the developing rat.
3,3'-Iminodipropionitrile (IDPN) has been demonstrated to produce a loss of hearing following both neonatal and adult exposures. Adult exposure induces a full spectrum hearing loss, whereas early postnatal exposure produces a high-frequency loss only. The purpose of this work was to delineate the period of development during which the rat becomes sensitive to the full ototoxic effects of IDPN. Primiparous Long Evans rats or their offspring were exposed to either saline or 300 mg/kg IDPN for three consecutive days. Ages of exposure were as follows: gestational days 15-17 or postnatal days (PND) 1-3, 5-7, 15-17, 20-22, 25-27, 30-32, 40-42, or 70-72. All animals were tested as adults for auditory thresholds to 5- and 40-kHz tones using reflex modification audiometry. Results demonstrate that adult-like susceptibility to IDPN was not reached until approximately PND 30-32. Early exposures (PND 5-22) to IDPN will induce a highfrequency selective hearing loss, sparing the lower frequency. Prenatal or early neonatal (PND 1-3) IDPN exposure resulted in a high degree of mortality (> 70%). The long period of time between the susceptible period for the high frequency (PND 5-7) and the lower frequency (PND 30-32) does not correspond to the basal to apical ontogenic profile of any one physiological or anatomical process. These data suggest either a unique site of action for IDPN in the cochlea or the possibility of two different mechanisms, one operating at early postnatal ages and one at later ages.
Goldey
E S
ES
Neurotoxicology Division, U.S. Environmental Protection Agency Research Triangle Park, NC 27711.
Kehn
L S
LS
Crofton
K M
KM
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001299:Audiometry; D001309:Auditory Threshold / Q000187:drug effects*; D003051:Cochlea / Q000187:drug effects* / Q000196:embryology; D005260:Female; D005865:Gestational Age; D034381:Hearing Loss / Q000139:chemically induced*; D006316:Hearing Loss, High-Frequency / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D008297:Male; D009498:Neurotoxins / Q000633:toxicity; D009570:Nitriles / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats
D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile