Acute ototoxicity of trialkyltins in the guinea pig.
Two trialkyltin compounds, trimethyltin chloride (TMT) and triethyltin bromide (TET) were evaluated for their acute effects on cochlear function in pigmented guinea pigs. Compound action potential (CAP) thresholds and 1 microV RMS cochlear microphonic (CM) isopotential curves were generated for 25 subjects following ip injection of TMT (2 mg/kg), TET (12 or 24 mg/kg) or inert vehicle (0.9% saline or 15% ethanol). The CAP is generated by the release of neurotransmitters from the inner hair cells and the subsequent depolarization of spiral ganglion cells. However, the sensitivity of the CAP is influenced by other cochlear structures including the outer hair cells which are thought to influence sensitivity of the inner hair cells. By contrast, CM reflects electromechanical function of the outer hair cells. CAP function was severely disrupted by organotin exposure while CM was unaffected by these agents. TMT administration impaired CAP thresholds at all frequencies within 30 min of administration. Thresholds deteriorated slightly more between 30 and 60 min. TET also reduced the sensitivity of the CAP to all frequencies. At the lower dose moderate impairments of function were observed at 30 min which became more noticeable at 60 min. Following 24 mg/kg TET injection, CAP sensitivity was markedly impaired even at 30 min. The CM isopotential values were not significantly altered 30 min or 60 min after either TMT or TET treatment at any of the 11 frequencies tested. These data document far more rapid toxic effects of TMT and TET than have been seen in most intact neuronal systems. They indicate that both organotins initially disrupt the functional integrity of either inner hair cells or spiral ganglion cells within the cochlea such that depolarization occurs only following a significant increase in stimulus intensity.
Clerici
W J
WJ
Department of Environmental Health Sciences, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205-2167.
Ross
B
B
Fechter
L D
LD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001300:Audiometry, Evoked Response; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D014267:Triethyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014267:Triethyltin Compounds; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride; C026405:bromotriethylstannane