Methodological evaluation of human research on asthmagenicity and occupational cleaning: a case study of quaternary ammonium compounds (“quats”)

Abstract

In this paper, we review methodological approaches used in studies that evaluated the association between occupational exposure to quaternary ammonium compounds (quats) and occupational asthma. This association is of interest because quats are a common active ingredient of disinfectants and have been linked to work-related asthma in some circumstances. However, any evidence-based assessment of an exposure-outcome association needs to consider both strengths and limitations of the literature. We focus on publications cited by various US and international organizations. Eighteen investigations included in the review fall into two broad categories: case reports and challenge studies of individual patients and population studies that examined the association between quats and asthma occurrence in groups of subjects. We evaluated these studies guided by questions that address whether: exposure data on specific quat(s) and other agents that may cause asthma were included, new asthma cases were differentiated from asthma exacerbation, and information on respiratory sensitivity versus irritation was given. We also assessed consistency across studies. Studies of individual patients, particularly those that provided detailed information on challenge test results, document cases of asthma induced by exposure to quats. By contrast, studies of occupational groups with the highest potential for quats exposure (e.g., cleaners and farmers) do not consistently report increased incidence of asthma due specifically to quats. The unresolved methodological issues include: poor understanding of exposure pathways considering that quats are non-volatile, lack of quantitative data allowing for identification of an asthmagenicity threshold, insufficient information on whether quats are sensitizers or act via dose-dependent irritation or some other mechanism, and inability to quantify risk of new-onset asthma attributable to quats. Another important area of uncertainty is the lack of information on the specific quats being used. There is also a lack of data capable of distinguishing the effects of quats from those of other chemical and biological workplace exposures. The current state-of-the-science does not allow a proper assessment of the potential link between quats and occupational asthma.

Progress in Occupational Asthma

“…OA induced by triclosan was documented by positive SIC [46]. A recent review evaluated the association between occupational exposure to quaternary ammonium compounds and OA and concluded that currently it is difficult to define this link in raison of the limited data in the literature, studies realized in specific populations (e.g., farmers or cleaners), poor understood pathogenesis and the presence of many confounders (other chemical and biological agents) in the workplace as possible asthmagens [48].…”

Quaternary Ammonium Compounds: Bioaccumulation Potentials in Humans and Levels in Blood before and during the Covid-19 Pandemic

“… 30 , 31 Human epidemiological studies on the health effects of exposure to QACs are limited and mostly include occupational exposure studies linking QACs to exacerbation of asthma-related symptoms. 37 − 39 In a recent study, the concentrations of BACs and DDACs in human blood were associated with the increase in inflammatory cytokines, decrease in the mitochondrial function, and disruption of cholesterol homeostasis in a dose-dependent manner at levels detected in the general population. 40 …”

Quaternary ammonium compounds: perspectives on benefits, hazards, and risk

“…The most complete assessment of the occupational asthma question was undertaken by LaKind and Goodman. 63 Among issues they grappled with were as follows:…”

“…With these in mind to guide their assessment, LaKind and Goodman (2019) 63 reported their review of 18 investigations, including population studies and both case reports and challenge studies of individual patients and assessed the association between QACs and asthma occurrence in various subject groups. Interestingly, they noted that "studies of occupational groups with the highest potential for QAC exposure (e.g., cleaners and farmers) do not consistently report increased incidence of asthma attributable to QACs."…”