title: Potentiation of noise-induced hearing loss by low concentrations of hydrogen cyanide in rats.
abstract: Noise-induced hearing loss is the most prevalent occupational injury in the United States despite the adoption of clear permissible exposure limits and protocols for hearing conservation. This study identifies low-level chemical asphyxiant exposure as a risk factor capable of potentiating noise-induced hearing loss. Rats were exposed to 10, 30, and 50 ppm hydrogen cyanide (HCN) alone for 3.5 h (n = 28) or in combination with 2 h octave band noise exposure (100 dB(lin); n = 28). Additional groups received noise exposure alone (n = 16) and no treatment other than placement in an inhalation chamber with clean air and quiet (n = 16). Pure tone compound action potential (CAP) thresholds were determined 4 weeks following the exposure in order to assess pure tone auditory sensitivity and permanent threshold impairment. Cochleae from an additional 13 subjects were processed for light microscopy to permit assessment of hair cell loss. The results demonstrate that the noise exposure alone impaired CAP threshold by about 10 dB, averaged between 12-40 kHz, and produced a 5% loss of outer hair cells at the base of the cochlea, but no inner hair cell loss. The combined exposure to noise and HCN caused a cyanide dose-dependent CAP threshold impairment that exceeds the noise exposure alone. This effect reached statistical significance at a HCN level of 30 ppm. Combined exposure also produced more outer hair cell loss than noise alone. HCN alone did not cause significant hearing loss or hair cell loss. A risk assessment analysis was conducted for the auditory threshold data using benchmark dose software published by the U. S. EPA (BMDS version 1.3). A continuous model showed that the data could be described by a linear function. For a benchmark response corresponding to a 5 dB increase in auditory threshold above the effect of noise alone, the lower bound on the 95% confidence interval for the benchmark dose was 9 ppm. The benchmark dose that impaired auditory threshold 10% above the effect of noise alone had a lower bound of 2 ppm. The lower bound to the HCN dose that produced a 1 SD elevation in noise-induced hearing loss was 16 ppm. These exposure levels provide a range of concentrations below to slightly above the short-term exposure limit for HCN. However, if these levels are adjusted for an 8 h time-weighted average (TWA), the resulting levels are below the permissible exposure level (PEL) for HCN.
authors.affiliation: Oklahoma Center for Toxicology, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 North Stonewall Street, Room 329, Oklahoma City, Oklahoma 73117, USA. fechter@ouhsc.edu
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Fechter
authors.forename: Guang-Di
authors.initials: GD
authors.lastname: Chen
authors.forename: David L
authors.initials: DL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects*; D006317:Hearing Loss, Noise-Induced / Q000209:etiology*; D006856:Hydrogen Cyanide / Q000633:toxicity*; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009622:Noise / Q000009:adverse effects; D051381:Rats; D020318:Rats, Long-Evans; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D006856:Hydrogen Cyanide