Ototoxicity

Turner Scientific is a leader in preclinical ototoxicity contract research

Hearing and balance assessments should not just be of interest to hearing scientists developing treatments for hearing disorders.

The ear is an untapped resource for drug development, toxicity screening, safety and reproductive toxicology work. Turner Scientific clients are able to more efficiently develop their pipeline compounds by evaluating the effects on the ears in early developmental stages. This allows for an estimation of general toxicity, while helping to avoid the side effects of hearing loss, imbalance, and tinnitus that are already common among FDA approved drugs.

Predictor of General Toxicity

Ototoxicity assessment is critical for safe and efficient drug development. Acting like a “canary in a coalmine”, the auditory and vestibular systems present an under-exploited sentinel prognosticator of general drug toxicity.​

  • Hair cells (the receptors for hearing and balance) are especially sensitive to toxins.
  • Hundreds of drugs, chemicals, and medical conditions are toxic to hair cells.
  • Hair cells are not capable of regenerating in humans.
  • The auditory nerve and central brain auditory structures are also sensitive to toxins.

Importance of Preclinical Ototoxicity Screening

Ototoxicity assessment is crucial to drug development given the prevalence and consequences of hearing loss and tinnitus

  • The World Health Organization estimates that hearing loss affects more than 5% of the world’s population (360 million people, including 32 million children).
  • Tinnitus (ringing in the ear) occurs in 25% of Americans every year with 8% experiencing tinnitus daily (Turner J et al, J Neurosci Res. 2012 July ; 90(7): 1480–1488).
  • Even mild hearing loss leads to significant consequences in pediatric and adult patient populations.
  • Preclinical (as opposed to clinical) screening for ototoxicity allows superior control of confounding variables, and use of more research tools to detect ototoxic damage.

Turner Scientific is dedicated to reduce damage to the auditory and vestibular organs, and to limit impairment to quality of life that accompanies these complications. Ototoxicity is common to many medications, chemicals, and medical conditions:

Medications

  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as aspirin, Ibuprofen
  • Aminoglycoside antibiotics such as kanamycin, neomycin, gentamycin
  • Additional antibiotics such as erythromycin, vancomycin, and many others
  • Diuretics such as furosemide, bumetanide
  • Chemotherapeutic (cancer) agents such as bleomycine, cisplatin, carboplatinum, methotrexate
  • Antimalarials such as chloroquine
  • Cardiac medications such as propanolol, quinidine
  • Anesthetics such as lidocaine, bupivacain
  • Psychopharmacologic agents such as amitryptiline, benzodiazepines, bupropion, fluoxetine, imipramine, lithium
  • Glucocorticoids such as prednisolone, ACTH
  • Thalidomide

Chemicals

  • Fuels (gasoline, diesel, kerosene, jet)
  • Carbon monoxide
  • Lead and derivatives
  • Toluene (solvent)
  • Xylene (solvent)
  • Styrene (plastics, rubber, resins)
  • Pesticides
  • Herbicides
  • Tricholoroethylene (solvent)
  • Dichloromethane (solvent)

Noise exposure and exposure to some of these chemicals (e.g., styrene, toluene, xylene) can have syergistic effects

Medical Conditions

  • Fetal Alcohol Syndrome
  • High fever, measles, chicken pox, HIV
  • Bacterial meningitis (leading cause of ototoxicity in infants and children)
  • Tumors, head trauma
  • Stroke and other blood flow disorders
  • Multiple congenital birth anomalies
  • In-utero pathogen exposure (cytomegalovirus, herpes, rubella, syphylis, toxoplasmosis)