Methylisothiazolinone Research Articles

Methylisothiazolinone modulates community assembly and improves syntrophic cooperation via adaptive evolution during sludge anaerobic digestion

Various antimicrobials could pose multifaced threats to anaerobic digestion (AD) of waste-activated sludge (WAS), yet it is still unclear how antimicrobials would affect the metabolic activity and assembly process of anaerobic microbiome. In this study, a typical antimicrobial, methylisothiazolinone (MIT), was introduced in AD and induced an initial lag effect on methane production that was eventually recovered. Although MIT disintegrated WAS to promote the release of bioavailable substrates from extracellular polymeric substances (EPS), it also caused adverse stress to the microbiome. The initial microbial metabolic activities and syntrophic relationships associated with methane generation were distinctly inhibited. Because the self-adaptive systems of two-component systems (e.g., ddpF, and ddpD) and quorum sensing (e.g., cheR, and cydB) were activated to restore the syntrophic interaction among functional anaerobes, metabolic activities were gradually recovered for methane generation. Ultimately, the methane-generation species (e.g., Methanobacterium, and Methanomassiliicoccus) were driven as core species by deterministic processes, while non-functional species (e.g., Nitrospirota) were marginalized by stochastic processes under MIT stress. Overall, this finding indicated the intrinsic drive of evolutionary adaptation, unraveled the community assembly process at phylogenetic level under antimicrobial stress, and gave direction on the assessment and mitigation of external contaminant-related ecological risks in WAS treatment.

Insight into the photodegradation of methylisothiazolinone and benzoisothiazolinone in aquatic environments

Methylisothiazolinone (MIT) and Benzisothiazolinone (BIT) are two widely used non-oxidizing biocides of isothiazolinones. Their production and usage volume have sharply increased since the pandemic of COVID-19, inevitably leading to more release into water environment. However, their photochemical behaviors in water environment are still unclear. Therefore, this study investigated photodegradation properties of MIT and BIT in natural water under simulated sunlight. The results demonstrated that direct photolysis was mainly responsible for their photodegradation which occurred through their excited singlet states rather than triplet states. The quantum yields of MIT and BIT photodegradation were 11 - 13.6 × 10−4 and 2.43 - 5.79 × 10−4, respectively. pH had almost no effect on the photodegradation of MIT, while the photodegradation of BIT was significantly promoted under alkaline condition due to abundance of BIT in its deprotonated form (BIT-N−). Cl−, NO3− and dissolved organic matter (DOM) in natural water inhibited the photodegradation of both MIT and BIT, with the light screening effect of DOM being the most significantly inhibitory factor. The addition of other isothiazolinones, which possibly coexisted with MIT and BIT in actual condition, slightly inhibited the photodegradation of MIT and BIT. The estimated half-life under natural sunlight at a 30°N latitude was estimated to be approximately 1.1 days. The photodegradation pathways of MIT and BIT are similar, primarily initiated from the ring-opening at the N-S bond, with Frontier electron densities (FED) calculations suggesting the likelihood of oxidation and ·OH addition reactions at the O, N, and S sites. While the photodegradation products exhibited significantly reduced acute toxicity compared to their parent compounds, they nonetheless posed substantial chronic toxicity. These insights are vital for assessing the ecological impacts of MIT and BIT in aquatic environments.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

Moving-bed biofilm reactor (MBBR) alleviates the negative effect of methylisothiazolinone on the nitrification-denitrification process

Methylisothiazolinone (MIT) is an emerging contaminant used as a biocide in housecleaning and skin care products. Therefore, MIT can reach civil wastewater treatment plants due to domestic usage, thus potentially inhibiting the biological process. This study aims to investigate, for the first time, the effect of MIT on the nitrification-denitrification process in a moving-bed biofilm reactor (MBBR). After a preliminary study performed in a fed-batch reactor, two MBBRs were simultaneously operated in semi-continuous mode for 136 days evaluating a concentration of MIT in the influent of 0.1 and 1.0 mg/L. A parallel study was also conducted under anaerobic conditions to evaluate the effect of MIT on methane production and volatile fatty acid accumulation. At a concentration of 0.1 mg MIT/L, the nitrification process experienced an initial complete inhibition. Subsequently, nitrifying bacteria gradually recovered, reaching approximately 49 % oxidation of ammonia nitrogen, a removal improved up to 64 % at 1.0 mg MIT/L. Although denitrification dealt with a temporary inhibition, the process ultimately achieved a 100 % decrease in nitrite and nitrate concentrations when the MIT concentration was increased from 0.1 to 1.0 mg/L. The cumulative methane yield reached approximately 134 mL CH4/g VS for the control group and was similar to the methane production obtained in the presence of MIT. A MIT removal of 100 % was achieved under aerobic, anoxic, and anaerobic conditions.

Influence of Surfactant on the Skin Permeation of Methylisothiazolinone and Methylchloroisothiazolinone.

Patch tests are often used in safety evaluations to identify the substance causing skin irritation, but the same substance can sometimes give positive or negative results depending on the test conditions. Here, we investigated differences in the skin penetration of two test compounds under different application conditions. We studied the effects of the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant polysorbate 80 (PS) on skin penetration of the preservatives methylisothiazolinone (MT) and methylchloroisothiazolinone (MCT), which are used in cosmetics such as shampoos. The skin permeation of MT was enhanced by SDS but was unchanged by PS. Skin impedance decreased in the presence of SDS whereas PS had the same effect as the control aqueous solution, suggesting that SDS reduction of the barrier function of skin affects the permeation of MT, a hydrophilic drug. Application of a mixture of MCT and MT in the presence of SDS did not affect the skin permeation of MCT whereas the permeation of MT was enhanced by SDS, indicating that the skin permeation of MCT is less affected by SDS than is MT. Thus, attention should be paid to the possible effect of co-solutes, especially hydrophilic drugs.

Methylisothiazolinone sensitisation in New Zealand is decreasing.

In the last 10 years methylisothiazolinone (MI) emerged as a global cause of preservative-related ACD. New Zealand has liberal regulations for the MI concentration limit in cosmetic products compared to Europe and Australia. The aim of this study was to evaluate the prevalence of MI sensitisation in New Zealand, explore sources of MI exposure and make recommendations on New Zealand regulations for MI use. This retrospective study included data from patients who underwent patch testing with MI from 2008 to 2021 in a tertiary hospital dermatology clinic and a private dermatology clinic in Auckland, New Zealand. Patient baseline characteristics were recorded along with results of patch testing. Sources of MI exposure were identified from medical records. Over the study period, 1049 patch tests were performed in 1044 patients. MI was only tested as a stand-alone allergen from 2015; positive reactions to MI increased from 5.3% in 2015 to a peak of 11.9% in 2017 and then decreased to 6.4% in 2021. The most common source of MI exposure was shampoo or conditioner (27.7% of all relevant reactions) followed by occupational exposures to paints, biocides or glue (19.1%). Both sensitisation and ACD to MI appear to be decreasing, likely secondary to changes in product compounding due to stricter concentration limits internationally. We recommend New Zealand adopt lower MI concentration limits for cosmetics to match the limits of Australia and Europe.

Influence of the TiO2 crystalline phase on the performance of UVA/brookite/persulfate and UVA/anatase/persulfate systems for the degradation of isothiazolinones in aqueous matrices

The activation of persulfate (PS) under UVA irradiation by two TiO2 polymorphs (brookite and anatase) and titanate photocatalysts was evaluated for the simultaneous removal of the biocides methylisothiazolinone (MIT) and chloromethylisothiazolinone (CMIT), in ultrapure water and real sewage treatment plant water (SW). Titania and titanate samples were synthesized by a hydrothermal method and characterized by XRD, SEM, N2 adsorption-desorption isotherms and UV-Vis DR. The reactions were performed in individual (brookite, anatase, titanate and PS) and hybrid (titania/PS and titanate/PS) systems and compared to those with TiO2-P25 as reference. In ultrapure water, the combined brookite/PS system showed a higher performance for MIT and CMIT abatement and a stronger synergistic effect between titania and PS than found in anatase/PS and titanate/PS systems, indicating the higher effectiveness of the brookite phase for PS activation under UVA. The use of SW water revealed the strong inhibitory effect of matrix constituents in the individual brookite, anatase and PS systems, which exhibited a low performance. However, the kinetics of MIT/CMIT in SW were greatly enhanced in the hybrid TiO2/PS systems, especially with brookite, leading to an efficient degradation of both pollutants and the decrease of total organic carbon (TOC). The addition of chemical scavengers showed a similar reactivity of HO• towards both isothiazolinones whereas a preferential attack of SO4•− to MIT was observed, demonstrating the selective nature of SO4•−.

Cobalt-doped SnS2 nanoplates for high-efficiency catalysis applications

The photocatalysis degradation of methyl iso thiazolinone (MIT) in water was effectively performed using cobalt-doped tin sulfide (Co–SnS2) nanoplates under UV irradiation. X-ray diffraction patterns (XRD) show that the crystallite size of nanoplates increases from 26 nm to 48 nm. Undoped SnS2 nanoplates exhibit plate-like nanostructure with smooth surfaces, with a size of 150–400 μm and a 50–70 nm thickness. Doping SnS2 nanoplates with cobalt increases the nanoplate's size to 300–600 nm. SnS2 and Co-doped SnS2 nanoplates have indirect bandgap energy with values of 1.95 and 1.86 eV, respectively. On the other hand, the electrical conductivity of SnS2 and Co-doped SnS2 nanoplates was 1.67×10−5S.cm−1 and 1.64×10−4S.cm−1, which increases to 6.54×10−4S.cm−1 and 1.25×10−2S.cm−1 upon UV irradiation, respectively. The higher degradation efficiency of a 5 mg/L concentration of MIT via SnS2 and Co–SnS2 nanoplates after 160 min is 66% and 91%, respectively. Finally, the photodegradation process was investigated using UV-VIS and FTIR analysis.

More than just methylisothiazolinone: Retrospective analysis of patients with isothiazolinone allergy in North America, 2017-2020

Isothiazolinones are a common cause of allergic contact dermatitis. To examine the prevalence of positive patch test reactions to isothiazolinones from 2017-2020 and characterize isothiazolinone-allergic (Is+) patients compared with isothiazolinone nonallergic (Is-) patients. Retrospective cross-sectional analysis of 9028 patients patch tested to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) 0.02% aqueous, MI 0.2% aqueous, benzisothiazolinone (BIT) 0.1% petrolatum, and/or octylisothiazolinone (OIT) 0.025% petrolatum. Prevalence, reaction strength, concurrent reactions, clinical relevance, and source of allergens were tabulated. In total, 21.9% (1976/9028) of patients had a positive reaction to 1 or more isothiazolinones. Positivity to MI was 14.4% (1296/9012), MCI/MI was 10.0% (903/9017), BIT was 8.6% (777/9018), and OIT was 05% (49/9028). Compared with Is-, Is+patients were more likely to have occupational skin disease (16.5% vs 10.3%, P <.001), primary hand dermatitis (30.2% vs 19.7%, P <.001), and be >40years (73.1% vs 61.9%, P<.001). Positive patch test reactions to >1 isothiazolinone occurred in 44.1% (871/1976) of Is+patients. Testing solely to MCI/MI would miss 47.3% (611/1292) of MI and 60.1% (466/776) of BIT allergic reactions. Retrospective cross-sectional study design and lack of follow-up data. Sensitization to isothiazolinones is high and concurrent sensitization to multiple isothiazolinone allergens is common.

Eluates from façades at the beginning of their service time affect aquatic and sediment organisms

Biocides are used in building materials to prevent microbial growth during storage (in-can preservatives) as well as after application (film preservatives). These compounds can leach out from the material into the environment and harm non-target organisms. In this study, the ecotoxicological effect of leachates at the beginning of a façade lifetime, on sediment and aquatic organisms was examined. For this purpose, leaching tests were carried out in the setting of a natural weathering experiment and a laboratory immersion with façade samples consisting of render/paint systems. The leaching experiments were performed with three different formulations, namely no biocides containing control, a formulation containing only in-can preservatives (benzisothiazolinone (BIT), methylchloroisothiazolinone (CMIT), and methylisothiazolinone (MIT)), and, as is common in organic building materials, containing both in-can and film preservatives (octylisothiazolinone (OIT) and terbutryn (TB)). In order to elucidate the effects of in-can and film preservative-containing eluates the toxicity of the generated leachables was evaluated on the model of several aquatic and sediment organisms, namely luminescent bacteria (Vibrio fischeri), green algae (Scenedesmus subspicatus), Salmonella typhimurium TA1535/pSK1002 (umu-test), fish-egg (Danio rerio), Chironomus riparius, and Lumbriculus variegatus. It was demonstrated that in-can preservatives leach out rapidly at the beginning of a façade lifetime and despite the short half-life of these compounds in aqueous solutions, they could be detected at high concentrations in the eluates. Furthermore, eluates from early sampling times, predominantly containing in-can preservatives, were found to cause toxic effects on sediment and aquatic organisms. The results demonstrate that in-can preservatives can impose a significant stress factor on the environment.

Synergy between UV light and trichloroisocyanuric acid on methylisothiazolinone degradation: Performance, kinetics and degradation pathway.

Methylisothiazolinone (MIT) is widely used in daily chemicals, fungicides, and other fields and its toxicity has posed a threat to water system and human health. In this study, ultraviolet (UV)/trichloroisocyanuric acid (TCCA), which belongs to advanced oxidation processes (AOP), was adopted to degrade MIT. Total chlorine attenuation detection proved that TCCA has medium UV absorption and a strong quantum yield (0.49 mol E−1). At a pH of 7.0, 93.5% of MIT had been decontaminated after 60 min in UV/TCCA system (kobs = 4.4 × 10−2 min−1, R2 = 0.978), which was much higher than that in the UV alone system and TCCA alone system, at 65% (1.7 × 10−2 min−1, R2 = 0.995) and 10% (1.8 × 10−3 s−1, R2 = 0.915), respectively. This system also behaved well in degrading other five kinds of contaminants. Tert-butanol (TBA) and carbonate (CO32−) were separately used in quenching experiments, and the degradation efficiency of MIT decreased by 39.5% and 46.5% respectively, which confirmed that HO• and reactive chlorine species (RCS) were dominant oxidants in UV/TCCA system. With TCCA dosage increasing in a relatively low concentration range (0.02–0.2 mM) and pH decreasing, the effectiveness of this AOP system would be strengthened. The influences of coexisting substances (Cl−, SO42−, CO32−, NO2− and NO3−) were explored. MIT degradation pathways were proposed and sulfur atom oxidation and carboxylation were considered as the dominant removal mechanisms of MIT. Frontier orbital theory and Fukui indexes of MIT were employed to further explore the degradation mechanism.

Methyl(chloro)isothiazolinone contact allergy: a monocentric experience from Turkey

Introduction Due to their ubiquitous use, isothiazolinones caused allergic contact dermatitis epidemics and their use was restricted by legal regulations. Objectives We aimed to evaluate demographic data, clinical findings, and patch test features of patients with methylisothiazolinone (MI) and/or methylchloroisothiazolinone(MCI) sensitivity in our study. Methods This study is a bidirectional and cross-sectional study, between July 2020 and September 2021. A total of 616 patients, including prospective and retrospective populations, demographic data, clinical findings, and patch test results were reviewed. Patients’ demographics, patch test results, allergen sources, presence of occupational contact, and the characteristics of dermatitis attacks were recorded. Results A total of 50 patients with MI and MCI/MI sensitivity, 36 male (72%) and 14 female (28%), were included in our study. The overall prevalence of MI and MCI/MI between 2014 and 2021 was 8.4% (52/616) with two peak levels in 2015(21%) and 2021 (20%). A statistically significant relationship was found between shampoo use and facial involvement (p = 0.031), shower gel use and arm involvement (p = 0.027), wet wipe use and hand involvement (p = 0.049), detergent use and the pulps (p = 0.026) and the lateral aspects of fingers involvement (p = 0.048), water-based dye use and periungual involvement (p = 0.047). Conclusion Although legal regulations related to MI and MCI/MI cause a decrease in the frequency of their sensitivities were still common causes of allergic contact dermatitis.

CD4+ T cells inhibit the generation of CD8+ epidermal-resident memory T cells directed against clinically relevant contact allergens.

CD8+ epidermal-resident memory T (TRM ) cells play central roles in local flare-up responses to experimental contact allergens by inducing massive influx of neutrophils to the epidermis upon allergen challenge. Whether similar immunopathogenic mechanisms are involved in the responses to clinically relevant contact allergens is unknown. The immune response to cinnamal, ρ-phenylenediamine (PPD) and methylisothiazolinone (MI) was studied in a well-established mouse model for allergic contact dermatitis that includes formation of TRM cells by ELISA, flow cytometry, fluorescence microscopy analyses and cell depletion protocols. We show that the formation of CD4+ and CD8+ epidermal TRM cells and the inflammatory response are highly allergen-dependent. However, the magnitude of the flare-up responses correlated with the number of epidermal CD8+ TRM cells, CXCL1/CXCL2 release and recruitment of neutrophils to the epidermis. Finally, depletion of CD4+ T cells strongly enhanced the number of epidermal CD8+ TRM cells, the flare-up response and the epidermal infiltration of neutrophils for all allergens. As the first, this study demonstrates that clinically relevant contact allergens have the ability to generate pathogenic, epidermal CD8+ TRM cells that recruit neutrophils following re-exposure to the allergen, but that this normally is counteracted by the simultaneous induction of anti-inflammatory CD4+ T cells.

Effects of stabilizer magnesium nirate on CMIT/MIT-induced respiratory toxicity

Despite a humidifier disinfectant (HD) product containing chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) with approximately 22% magnesium nitrate as a stabilizer, no report on the effects of magnesium nitrate on the respiratory toxicity of CMIT/MIT is available. In this study, Kathon CG and Proclin 200, containing approximately 1.5% CMIT/MIT with different magnesium nitrate concentrations (22.6% and 3%, respectively), were used to compare respiratory effects after intratracheal instillation (ITI) in C57BL/6 mice. C57BL/6 mice were randomized into groups of saline control, magnesium nitrate, Kathon CG, and Proclin 200 with 1.14 mg/kg of CMIT/MIT as the active ingredient, and administration was performed 6 times in a 2–3 day-interval in 2 weeks in all groups. Differential cell count analysis, cytokine analysis, and histological analysis of lung tissue were performed to characterize the injury features. Both Kathon and Proclin 200 induced an increase in inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid, in particular, eosinophils and type 2 T helper cell (Th2)-secreted cytokines. All histopathological changes including granulomatous inflammation, mixed inflammatory cell infiltration, mucous cell hyperplasia, eosinophil infiltration, and pulmonary fibrosis were induced with similar frequency and severity in Kathon CG and Proclin 200 groups. Our results suggested that magnesium nitrate did not affect CMIT/MIT-induced lung injury in the intratracheally instilled model. Further inhalation studies are needed to determine the distribution and toxicity differences of CMIT/MIT in the lungs according to the magnesium nitrate concentration.

Quantification of Methylisothiazolinone and Methylchloroisothiazolinone Preservatives by High-Performance Liquid Chromatography.

Isothiazolinone preservatives (methylisothiazolinone (MIT) and methylchloroisothiazolinone (CMIT) are commonly used in cosmetics, industrial and household products. However, these isothiazolinone derivatives are known to cause allergic contact dermatitis. Hence, a sensitive, accurate, and reliable method for the detection of these compounds is thus warranted. The study aims to analyze concentrations of MIT and CMIT by high performance liquid chromatography. The analytical method used for quantification of MIT and CMIT in cosmetic products (leave-on-baby wet wipes) complies with the validation acceptance criteria (international standards ISO 5725, EU25 European Union for cosmetic regulations). MIT and CMIT were extracted and analyzed in leave-on baby wet-wipes collected from different stores in Riyadh city. Extraction was performed by ultrasonication of the samples, solid-phase extraction, and liquid-liquid extraction. Ten (10) µL of the sample was injected into the HPLC system and samples were analyzed with a mixture of acetic acid and methanol (80:20 v/v) in an isocratic mode. The flow rate was maintained at 1 mL/min. UV detection was performed at 274 nm. The results demonstrated recoveries between 90 and 106%, measurement uncertainty of C +/- 0.4% for methylisothiazolinone and C +/- 0.03% for methylchloroisothiazolinone, repeatability limit (r = 0.2%) and intermediate precision limit; R = 2% and R2 of 0.9996.

Occupational contact allergy: The European perspective-Analysis of patch test data from ESSCA between 2011 and 2020.

Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n= 46 652) in whom an occupational causation was refuted served as comparison group. The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives.

North American Contact Dermatitis Group Patch Test Results: 2019-2020.

Background: Patch testing is an important diagnostic tool for assessment of allergic contact dermatitis (ACD). Objective: This study documents the North American Contact Dermatitis Group (NACDG) patch testing results from January 1, 2019, to December 31, 2020. Methods: At 13 centers in North America, patients were tested in a standardized manner with a screening series of 80 allergens, and, as indicated, supplemental allergens. Results: Overall, 4121 patients were tested; 2871 (69.7%) had at least 1 positive/allergic patch test reaction and 2095 patients (51.2%) had a primary diagnosis of ACD. The most commonly positive allergens were nickel (18.2%), methylisothiazolinone (MI) (13.8%), fragrance mix (FM) I (12.8%), hydroperoxides of linalool (HPL) (11.1%), and benzisothiazolinone (BIT) (10.4%). Compared with that of 2017-2018, prevalence of top 20 allergens statistically increased for FM I, HPL, BIT, propolis, and hydroperoxides of limonene (3.5%). For the first time, MI positivity did not increase between reporting periods. Approximately one-fifth of patients (20.3%) had ≥1 clinically relevant reaction(s) to allergens/substances not on the NACDG series. Conclusions: The epidemic of MI contact allergy in North America may have reached a plateau. Patch testing using a robust screening series, and supplemental allergens as indicated, is necessary for comprehensive evaluation of ACD.

Trends in the Prevalence of Methylchloroisothiazolinone/Methylisothiazolinone Contact Allergy in North America and Europe

The common use of isothiazolinones as preservatives is a global cause of allergic contact dermatitis. Differences in allowable concentrations of methylisothiazolinone (MI) exist in Europe, Canada, and the US. To compare the prevalence of positive patch test reactions to the methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) combination and MI alone in North America and Europe from 2009 to 2018. This retrospective analysis of North American Contact Dermatitis Group, European Surveillance System on Contact Allergies (ESSCA), and the Information Network of Departments of Dermatology (IVDK) databases included data from patients presenting for patch testing at referral patch test clinics in North America and Europe. Patch tests to MCI/MI and MI. Prevalence of allergic contact dermatitis to MCI/MI and MI. From 2009 to 2018, participating sites in North America and Europe patch tested a total of 226 161 individuals to MCI/MI and 118 779 to MI. In Europe, positivity to MCI/MI peaked during 2013 and 2014 at 7.6% (ESSCA) and 5.4% (IVDK) before decreasing to 4.4% (ESSCA) and 3.2% (IVDK) during 2017 and 2018. Positive reactions to MI were 5.5% (ESSCA) and 3.4% (IVDK) during 2017 and 2018. In North America, the frequency of positivity to MCI/MI increased steadily through the study period, reaching 10.8% for MCI/MI during 2017 and 2018. Positive reactions to MI were 15.0% during 2017 and 2018. The study results suggest that in contrast to the continued increase in North America, isothiazolinone allergy is decreasing in Europe. This trend may coincide with earlier and more stringent government regulation of MI in Europe.

Electrochemical Characterization and Voltammetric Determination of Methylisothiazolinone on a Boron-Doped Diamond Electrode.

The electrochemical properties of methylisothiazolinone (MIT), the most widely used preservative, were investigated by cyclic (CV) and differential pulse voltammetry (DPV) to develop a new method for its determination. To our knowledge, this is the first demonstration of a voltammetric procedure for the determination of MIT on a boron-doped diamond electrode (BDDE) in a citrate-phosphate buffer (C-PB) environment. The anodic oxidation process of methylisothiazolinone, which is the basis of this method, proved to be diffusion-controlled and proceeded with an irreversible two-electron exchange. The radical cations, as unstable primary products, were converted in subsequent chemical reactions to sulfoxides and sulfones, and finally to more stable final products. Performed determinations were based on the DPV technique. A linear calibration curve was obtained in the concentration range from 0.7 to 18.7 mg L-1, with a correlation coefficient of 0.9999. The proposed procedure was accurate and precise, allowing the detection of MIT at a concentration level of 0.24 mg L-1. It successfully demonstrated its suitability for the determination of methylisothiazolinone in household products without the need for any separation steps. The proposed method can serve as an alternative to the prevailing chromatographic determinations of MIT in real samples.

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019-2021 epidemiological situation.

Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. We analysed all 2019-2021 consecutive patients patch-tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI-positive patients were positive to BIT, whereas one in five BIT-positive patients were positive to MI. Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon.