Evaluating the Risk of Ototoxicity Due to Metals Exposures

Abstract

Hearing is vital for speech communication and evaluation of the environment. Damage to this sense harms both physical and social health; poor learning outcomes can also arise. Noise is a well-known exposure that can result in hearing loss (HL), but other environmental exposures in combination with noise may also impact HL. Previous studies have suggested that exposures to toxic metals are associated with HL, while essential elements show protective benefits. This dissertation used three studies to explore the relationship between metal exposures and HL, and accounted for exposure mixtures and protective elements.

First, a controlled laboratory experiment treated mice with lead (Pb) and cadmium (Cd), both alone and in tandem, in drinking water for twelve weeks. Auditory outcomes were measured following treatment with chemical toxicants in addition to the physical agent, noise. Dosing with Pb and Cd reached relevant occupational exposure levels: mean blood levels were 60.1 μg/dL for Pb and 27.2 μg/L for Cd. Animals displayed mean threshold shifts of 42 dB at 32 kHz following noise exposures of 105 dB. However, threshold shifts were not significantly different from controls after treatment with Pb or Cd alone. Combinations of exposures to Pb and noise, Cd and noise, as well as all three toxicants together did not cause threshold shifts significantly different than noise alone. This adult CBA/CaJ mouse model demonstrated a lack of ototoxicity due to Pb and Cd exposure.

Second, a case-control study of newborn infants born between 2003 and 2015 investigated auditory impacts associated with blood levels of Pb and methylmercury (MeHg). Cases with abnormal hearing screenings were matched to controls with normal hearing screenings. Dried blood spots collected after birth were analyzed for MeHg and Pb, in addition to the essential elements calcium, copper, iron, potassium, selenium, and zinc. Conditional logistic regression models of exposure quartiles showed a significant trend (p=0.03) with increasing levels of dried blood MeHg increasing the odds of a hearing screening failure (OR=1.81, 95% CI 1.01-3.24). Models also indicated a significant association with increasing levels of calcium decreasing the odds of hearing screening failure (OR=0.49, 95% CI 0.34-0.70). A significant interaction between selenium and zinc was also noted in logistic regression models.

Third, a cross-sectional study in a developing nation investigated Pb and other toxicant metals (arsenic, cadmium, manganese, and MeHg), along with essential elements (copper, iron, selenium, and zinc), and noise exposures in a potentially vulnerable community of electronic waste (e-waste) recycling workers. This study recruited 58 e-waste workers, with an average age of 26, from their worksite in Agbogbloshie, Ghana. Sixty percent of participants were observed to have a noise notch, or elevated hearing thresholds at high frequencies. Potentially harmful levels of noise exposure were observed during both occupational and non-occupational tasks. A metric quantifying the variety of work tasks improved multivariate regression models predicting the degree of hearing impairment at high frequencies. Essential elements were not significantly associated with levels of toxicant metals or HL. However, a significant interaction between levels of zinc and noise was observed.

Taken together, these studies do not provide consistent evidence of an ototoxic impact from Pb or Cd exposure; however, MeHg ototoxicity was significant. The three studies also did not find significant evidence of interactions between toxicant metals and noise. Nonetheless, Pb and Cd exposures can damage other tissues relevant to public health.