Experimental studies on acute health effects of acrolein and other aldehydes

Aldehydes are reactive and ubiquitous in indoor as well as outdoors and can give rise to significant health problems in humans, e.g. irritation of the eyes and toxic effects on the upper respiratory tract. This thesis focuses on the irritating and inflammatory properties of three commonly occurring aldehydes; acrolein, crotonaldehyde and hexanal.

Male and female volunteers were exposed in a controlled environment at six occasions for 2 hours to clean air only, 15 ppm ethyl acetate (EA) only and 0.05 ppm and 0.1 ppm acrolein with and without EA (Paper I). No significant exposure-related adverse effects (pulmonary function, nasal swelling, and inflammatory markers, coagulation markers, cell differentials, breathing frequency, symptom ratings except eye irritation) were found. The ratings of eye irritation were slightly but significantly increased during exposure to 0.1 ppm acrolein alone as well as combined with EA. Blinking frequency was only increased at 0.1 ppm acrolein alone.

Employing a novel olfactometer developed in-house, we determined odor (OT) and lateralization (LT) thresholds in naïve subjects (Paper II). The median OTs was similar to or lower than previously reported: 17 ppb (acrolein), 0.8 ppb (crotonaldehyde) and 97 ppb (hexanal).

We compared pulmonary pro-inflammatory and oxidative stress responses in seven inbred strains of mice after 11 weeks of whole body exposure to 1 ppm acrolein with filtered air as the control (Paper III). The responses varied widely between strains, and were in general agreement with that expected from previously reported survival times in the same mouse strains after acute exposure to 10 ppm acrolein.

The inflammatory and toxic effects of acrolein (0-0.5 ppm), crotonaldehyde (0-5 ppm) and hexanal (0-50 ppm) were further studied in a newly developed exposure system allowing for airborne exposure of differentiated human pulmonary bronchial epithelial cells (PBEC) co- cultured with fibroblasts at an air- liquid interface (Paper IV). The release of inflammatory markers and the corresponding mRNA expressions increased. These effects were not observed with exposure of PBECs under submerged conditions.

The findings herein provide new insights in the acute effects of environmentally realistic exposure-concentrations of acrolein, crotonaldehyde and hexanal. The results may prove helpful in future risk assessment and risk management efforts, such as setting health-based occupational exposure limits.

List of scientific papers

I. Aishwarya M. Dwivedi, Gunnar Johanson, Johnny C. Lorentzen, Lena Palmberg, Bengt Sjögren and Lena Ernstgård. Acute effects of acrolein in human volunteers during controlled exposure. Inhalation Toxicology. 2015; 27 (14); 810-821.
https://doi.org/10.3109/08958378.2015.1115567

II. Lena Ernstgård, Aishwarya M. Dwivedi, Johan N. Lundström and Gunnar Johanson. Measures of odor and lateralization threshold of acrolein, crotonaldehyde and hexanal using a novel vapor delivery technique. PLoS One. 2017 26; 12 (9): e0185479.
https://doi.org/10.1371/journal.pone.0185479

III. Swapna Upadhyay, Aishwarya M. Dwivedi, Lena Ernstgård, Lena Palmberg, Lung Chi Chen, Karen Galdanes, Terry Gordon and Gunnar Johanson. Variation of inflammatory and oxidative stress responses among inbred mouse strain following sub-chronic inhalation exposure to acrolein. [Manuscript]

IV. Aishwarya M. Dwivedi, Swapna Upadhyay, Gunnar Johanson, Lena Ernstgård and Lena Palmberg. Inflammatory effects of acrolein, crotonaldehyde and hexanal vapors on human bronchial epithelial cells cultured at air-liquid interface. Toxicology in Vitro. 2017; (46) 219-228.
https://doi.org/10.1016/j.tiv.2017.09.016