Synergistic interaction of co-exposure to humidifier disinfectant chemicals CMIT/MIT and PHMG in lung injury.

ABSTRACT

A number of biocidal disinfectant chemicals are used as household products to prevent spread of pathogens. People are commonly exposed to multiple chemicals through those disinfectants. However, effects of interactions (e.g., synergism) between disinfectants on human health outcomes have been rarely studied. In this study, we aimed to investigate associations of a mixture of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) and polyhexamethylene guanidine (PHMG), which had been used as humidifier disinfectants (HDs) in South Korea, with HD-associated lung injury (HDLI) in a Korean population (n = 4058) with HD exposure through use of HD products. Exposure to HD was retrospectively assessed by an interview-based standardized survey, and HDLI was determined by clinical assessment. After adjusting for covariates, PHMG-specific exposure indices (e.g., amount of use, indoor air concentration, and weekly exposure level) were dose-dependently associated with HDLI (their odds ratios for the comparison of third tertile versus first tertile were 1.95, 1.77, and 2.16, respectively). CMIT/MIT exposure was not observed to have a significant association with HDLI in a single chemical exposure model; however, associations between PHMG exposure and HDLI were strengthened by co-exposure to CMIT/MIT in combined chemical exposure models, where synergistic interactions between CMIT/MIT use and PHMG indices (amount of use and weekly exposure level) were observed (p-interaction in additive scale 0.02 and 0.03, respectively). Our findings imply that adverse effects of PHMG exposure on lung injury among HD users might be worsened by co-exposure to CMIT/MIT. Given that plenty of household products contain disinfectants on global markets, epidemiological and toxicological investigations are warranted on interaction effects of co-exposure to disinfectants.