Methylisothiazolinone: Dermal and respiratory immune responses in mice

• Published in: Toxicology letters Vol. 235; no. 3; pp. 179 - 188
• Main Authors: Devos, Fien C., Pollaris, Lore, Van Den Broucke, Sofie, Seys, Sven, Goossens, An, Nemery, Benoit, Hoet, Peter H.M., Vanoirbeek, Jeroen A.J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 15.06.2015
• Subjects: Airways; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Asthma - chemically induced; Chemical-induced asthma; Cosmetics; Dose-Response Relationship, Drug; Ear; Gene Expression Regulation - immunology; Immunoglobulin E - genetics; Immunoglobulin E - metabolism; Irritation; Lymph; Male; Methylisothiazolinone; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Preservatives; Preservatives, Pharmaceutical - administration & dosage; Preservatives, Pharmaceutical - chemistry; Preservatives, Pharmaceutical - toxicity; Sensitizer; Skin - immunology; Skin/lung; T-Lymphocyte Subsets; Thiazoles - administration & dosage; Thiazoles - chemistry; Thiazoles - toxicity; Vehicles; Chemical-induced asthma; Methylisothiazolinone; Mice; Sensitizer; Skin/lung
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2015.04.009

•Dermal treatment with methylisothiazolinone results in sensitization.•An airway challenge with methylisothiazolinone induces sensory irritation.•Methylisothiazolinone is not an asthmogen in this experimental setup. Methylisothiazolinone (MI), a widely used chemical preservative in industrial and household products, and cosmetics, has been associated with allergic contact dermatitis. However, the asthmogenic capacity of MI is currently unknown. In this study, we investigated the capacity of MI to elicit asthma-like responses in a validated mouse model. On days 1 and 8, mice (C57Bl/6 and BALB/c) were dermally treated with MI or vehicle on each ear. On day 15, mice received a single intranasal challenge with MI or vehicle. Immediately after the challenge, the early ventilatory response was measured using a double chamber plethysmograph. One day later, airway hyperreactivity, pulmonary inflammation and immune-related parameters were assessed. Dermal treatment with MI in both C57Bl/6 and BALB/c mice induced increased T- and B-cell proliferation in the auricular lymph nodes, along with IFN-γ production and limited increases in total serum IgE, confirming dermal sensitization. An airway challenge with MI led to an early ventilatory response (decreased breathing frequency), indicative for acute sensory irritation. However, 24h later no allergic respiratory response (no airway hyperreactivity (AHR) nor pulmonary inflammation) was found in either mouse strains. Our study indicates that MI can be classified as a strong dermal sensitizer and irritant, but not an asthmogen after initial dermal sensitization, followed by an airway challenge.