Contact Dermatitis • Contact Points
MCI AND MI STRUCTURE–ACTIVITY RELATIONSHIP • STINGENI ET AL.
An Italian multicentre study on
sensitivity: understanding the structure–activity relationship
, Leonardo Bianchi
, Caterina Foti
, Paolo Romita
, Luigi Rigano
and Katharina Hansel
on behalf of the MCI/MI SIDAPA network
Clinical, Allergological and Venereological Dermatology Section, Department of Medicine, University of Perugia, 06129 Perugia, Italy,
Biomedical Science and Human Oncology, Dermatological Clinic, University of Bari, 70124 Bari, Italy and
R&D Department, Institute of Skin and Product
Evaluation, 20125 Milan, Italy
Key words: chemical structure; cross-reaction; impurity; MCI/MI; methylchloroisothiazolinone;
methylisothiazolinone; MI; patch test; primary sensitizer; structure –activity relationship.
The mixture methylchloroisothiazolinone (MCI)/
methylisothiazolinone (MI) is a well-known contact
sensitizer (1). However, studies to determine the pri-
mary sensitizer in this blend are rare, and have been
performed only in small groups of patients (2–4). Herein,
we present a larger study on humans in which we used
the structure–activity relationship of the molecules to
explain (i) why MCI is the stronger allergen, and (ii) why
cross-reactivity between MCI and MI can be expected.
Materials and Methods
From January 2016 to December 2016, eight
patch-testing Italian clinics conducted a study on 141
patients (34 men and 107 women; mean age 44.1 years)
recently found to be sensitized to MCI/MI 0.02% aq.
We recalled patients with positive patch test reactions
to MCI/MI during the period 2014–2016, mainly
resulting from non-occupational exposure (cosmetics).
Correspondence: Luca Stingeni, Department of Medicine, Section of Clin-
ical, Allergological and Venereological Dermatology, University of Perugia,
06156 Perugia, Italy; Polo Ospedaliero-Universitario Santa Maria della Miseri-
cordia, Sant’Andrea delle Fratte, 06156 Perugia, Italy. Tel: +39 0755783452;
Fax: +39 0755783498. Email: email@example.com
Members of the MCI/MI SIDAPA network and contributors. The follow-
ing collaborators contributed data to this analysis: Silvia Mariel Ferrucci
(Ospedale Maggiore Policlinico, Milano); Monica Corazza (Ferrara); Cataldo
Patruno (Napoli); Massimo Gola (Firenze); Donatella Schena (Verona); and
Paolo Pigatto (Milano University)
Conﬂicts of interest: All authors have no interests to report.
Funding sources: This study was supported in part by a grant from the Società
Italiana di Dermatologia Allergologica Professionale e Ambientale (SIDAPA).
The patients were patch tested with MCI and MI at
the same concentrations as in the blend: MCI 0.015%
aq. (provided by the Laboratory of the Department of
Occupational and Environmental Dermatology, Lund
University, Malmö, Sweden) and MI 0.005% aq. (FIRMA,
Florence, Italy). We also tested MI 0.2% aq. (FIRMA) (1,
5). In this study, micropipettes were used for dosing, and
haptens (0.2 ml) were simultaneously applied. Occlusion
was performed for 2 days with Haye’s Test Chambers
(Haye’s Service, Alphen aan den Rijn, The Netherlands)
tape (Artsana, Grandate, Italy), and evaluation
was performed on day (D) 2, D4, and D7, according to
ESCD guidelines (6).
The patch test results are shown in Fig. 1. One hundred
and ten subjects (78.1%) reacted to MCI: 60 (42.6%)
reacted only to MCI, and 50 (35.5%) reacted to both MCI
and MI. Only 16 (11.3%) subjects reacted only to MI.
Fifteen subjects (10.6%) reacted neither to MI nor to MCI.
As previously reported (2, 4, 7, 8), MCI was found to be
the stronger sensitizer, which shows that primary sen-
sitization to MCI still occurs, although the amount of
exposure to MCI through MCI/MI via cosmetics and in
occupational settings has become rather low. This cannot
be explained by simple structural analysis, as this shows
similar polarization of negative charges (electron cloud
accumulation) around the oxygen atom (O) in MCI and
MI, although positive charges (electron-decient areas)
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis, 78, 287–306