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Abstract

Background: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) contact dermatitis is a severe problem. The high concentrations of these substances and other isothiazolinones such as benzisothiazolinone (BIT) and octylisothiazolinone (OIT) contained in cleaning products may cause allergic contact dermatitisin sensitized patients. Objectives: To evaluate the exposure to isothiazolinones contained in cleaning products on the market and from sensitized patients, and verify the accuracy of labelling. Methods: A total of 34 cleaning products were collected (17 supplied by sensitized patients and 17 bought randomly). Analysis was made of the concentrations of MI, MCI, BIT and OIT using liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: MI and BIT were the components most frequently detected. Of all the products analyzed, 76.5% contained at least one isothiazolinone. Twelve products had a MI concentration above the permitted level for rinse-off cosmetics. Most of them were coming into direct contact with the skin in daily use. Mislabelling occurred in 8 products. Conclusions: Some cleaning products with high concentrations of isothiazolinones may cause cutaneous symptoms in sensitized patients, especially in spray form. The labelling should be correct, also regarding the use of each article. This article is protected by copyright. All rights reserved.

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... [36][37][38] In cleaning products, isothiazolinones, including benzisothiazolinone (BIT) and octylisothiazolinone may be found in high concentration, beyond what can be rinsed off. 39 In 1 study of 34 products, 17 of which were selected at random, 76.5% contained at least 1 isothiazolinone, with MI and BIT most frequently detected by means of mass spectroscopy. 39 BIT is not tested in routine patch test series; thus, clinicians should have a high index of suspicion. ...
... 39 In 1 study of 34 products, 17 of which were selected at random, 76.5% contained at least 1 isothiazolinone, with MI and BIT most frequently detected by means of mass spectroscopy. 39 BIT is not tested in routine patch test series; thus, clinicians should have a high index of suspicion. 39 Parabens Parabens are preservatives found in topical formulations and personal care products, such as sunscreens and cosmetics. ...
... 39 BIT is not tested in routine patch test series; thus, clinicians should have a high index of suspicion. 39 Parabens Parabens are preservatives found in topical formulations and personal care products, such as sunscreens and cosmetics. They are weak sensitizers when compared with MCI/MI, and as such, were named the American Contact Dermatitis Society's nonallergen of the year in 2019 owing to their low sensitization rate. ...
Article
Objective: Reading this article will familiarize the reader with the mechanisms and causes of contact dermatitis. Data sources: Recent research articles, relevant review articles, and case series/reports in English from PubMed database mostly from 2010 onwards. Study selections: Most data was in the form of retrospective studies. Efforts were made to include clinical trials; however, for newer allergens and data on biologics, case series and case reports were included. Older studies regarding mechanism were included if they were of particular importance. Results: An understanding of this review should enable the reader to approach the patient with unknown dermatitis with a better understanding of cause and management. Conclusion: Clinical suspicion for relevant allergens combined with interpretation of patch tests are important in the diagnosis and treatment of patients with contact dermatitis.
... Further research is necessary to refine the estimated dermal loads concerning CMI exposure. Marrero-Alemán et al. (2020), Garcia-Hidalgo et al. (2017) and Ezendam et al. (2018), and the MI-equivalent concentration calculated from these data. Thomsen et al. (2018), Schwensen et al. (2015), Goodier et al. (2018) Measurements and literature (see Table A3) Product amount 0.53 g Cleaning Products Fact Sheet Measurements and literature (see Table A3) ...
... Overall measured concentrations of MI and CMI in shower gel/foam/scrub derived from NVWA data, and the MI-equivalent concentration calculated from these data used for the exposure assessment for children.Table A3Overall measured concentrations of MI and CMI in laundry product derived from NVWA data andMarrero-Alemán et al. (2020),Garcia-Hidalgo et al. (2017), and the MI-equivalent concentration calculated from these data. ...
Technical Report
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Isothiazolinones are preservatives. They are frequently used in, for example, personal care products like sunscreen and shampoo, as well as cleaning products, paint and aqueous toys like clay and toy slime. They ensure that a product does not spoil and that its shelf life is prolonged. If people come into contact with isothiazolinones, this could lead to allergic reactions of the skin. Currently, consumers are advised to be cautious with these substances (see http://www.waarzitwatin.nl). In order to assess the risk of allergic reactions, the extent to which people are exposed to these substances should be determined. RIVM has investigated this by calculating the exposure to isothiazolinones. This investigation was carried out by estimating to which extent various product groups contributed to the total exposure, as people can be exposed to isothiazolines via various different products every day. The total exposure in both adults and children has been investigated for three widely-used substances: methylisothiazolinone, chloromethylisothiazolinone and benzisothiazolinone. The results of this investigation indicated that, in some cases, the total exposure is higher than the safe amount. More research is needed to know whether this is really the case. For example, for many products the exact amount of isothiazolinones they contain is unknown. In addition, it is not always determined how many people use such products and how often. It should also be investigated whether other types of isothiazolines, such as dichlorooctylisothiazolinone and octylisothiazolinone, contribute to the total exposure to isothiazolinones. The NVWA has measured the amount of isothiazolinones in hundreds of different products. RIVM used these measurements to calculate the exposure using the PACEM and ConsExpo computer models. ConsExpo can provide a first estimation of the exposure that occurs when a person uses a single product. With PACEM, exposure to multiple products can be calculated. Furthermore, PACEM gives a more realistic estimation of the exposure, because it uses concrete data about the frequency of use. Keywords: aggregate exposure, PACEM, ConsExpo, personal care products, cosmetics, household cleaning products, preservatives, isothiazolinones, MI, CMI, BIT
... Isothiazolinone (IT) biocides are antibacterial substances commonly used as preservatives or disinfectants in commercial products [1,2]. Although the use of antibacterial substances is increasing globally, the systemic effects of IT biocides on human health are poorly understood [3][4][5][6]. These biocides can be absorbed orally and dermally during personal and industrial use [7][8][9] and subsequently circulate in the blood posing a human health risk [2,10,11]. ...
... (b) Caspase-3 activity was examined at 3 h after treatment with 0, 5, or 25 μM OIT (n = 4). (c and d) The extents of (c) MTT reduction and (d) LDH release were examined at 0, 1, 3, 6, and 24 h after treatment with 0, 5, or 25 μM OIT (n = [3][4][5][6]. (e,f) Functional changes in endothelial permeability were analyzed by TEER measurements (e) and an in vitro FITC-dextran (m.w. ...
Article
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Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood-brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.
... The wide usage of isothiazolinones as preservatives has resulted in occupational exposure in other professions as well. Numerous reports of these substances in cleaning products place cleaning professionals at particular hazard [86,87]. Products used in metalworking may also contain isothiazolinones, including emulsifying oils and stainless steel aerosol sprays [88,89]. ...
Article
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Purpose of Review This article aims to summarize some recent trends in occupational allergic contact dermatitis (ACD), including dermatitis related to pandemic-level personal protective equipment in healthcare workers, hazards patients may experience when working from home, and occupational perspectives on the recent American Contact Dermatitis Society (ACDS) allergens of the year and ACDS Core Allergen Series updates. Recent Findings Recent ACDS Allergens of the Year may be particularly relevant to healthcare workers, including isobornyl acrylate, which is present in glucose sensors and propylene glycol present in hand cleansers and disinfectants. Lavender, limonene, and linalool, all of which are new additions to the ACDS Core Allergen Series, have been reported as causes for occupational ACD in massage therapists and aromatherapists. Isothiazolinone allergy continues to rise in both consumer and occupational settings. Finally, the COVID-19 pandemic has resulted in a wave of occupational ACD in healthcare workers to personal protective equipment, and revealed new potential allergens for individuals working from home. Summary Occupational allergic contact dermatitis continues to exert a significant occupational disease burden. Remaining aware of the current trends in allergens may allow for earlier recognition, diagnosis, and treatment, subsequently helping our patients to work in healthier and safer environments.
... 112 Sources include rinse-off products such as shampoos, conditioners, soaps, nail polish, 113 laundry detergents, 104 and household cleaning products. 114,115 MI is also found in paints and glues, explaining numerous cases of hand dermatitis from homemade slime containing these preservatives. 34 ...
Article
Allergic contact dermatitis (ACD), a delayed hypersensitivity skin reaction to environmental allergens, has a prevalence that is similar in children and adults. However, diagnostic testing for ACD in pediatric populations accounts for less than one-tenth of all patch tests. The relative infrequency of pediatric patch testing may be attributed to the difficulty in testing in this population, which includes a smaller surface area for patch test placement and maintaining cooperation during patch testing especially in younger children. Diagnosis can be difficult in children, as the appearance of ACD can mimic other common pediatric skin conditions, particularly atopic dermatitis and irritant contact dermatitis. Comprehensive history-taking, guided by patient presentation, age group, and location of dermatitis, helps build clinical suspicion. Such clinical suspicion is one of the major reasons behind patch testing, with additional indications being recalcitrant dermatitis and dermatitis with atypical distribution. U.S. pediatric data has revealed the top allergens to be metals, fragrances, topical antibiotics, preservatives, and emollients. These trends are important to recognize to guide management and accurate diagnosis, as ACD tends to persist if the allergen is not identified and can affect patients’ quality of life.
Article
People are exposed to various chemicals contained in consumer products for which the risks are poorly characterized. There is growing evidence that exposure to endocrine disrupting chemicals (EDCs) through product use potentially affects development, behavior, and reproduction. However, limited information is available about common combinations of chemicals based on their appearance and potential health effects. The present study listed the ingredients contained in 11064 household chemical products from a publicly available database, and identified EDCs related to estrogenicity, androgenicity, thyroid hormone disruption, and changes in steroidogenesis. Association rule mining was applied to the dataset to identify frequent combinations of chemicals or commonly occurring EDCs contained in a single product. Among the target products, ingredient names were matched with 1241 chemical identifiers. A total of 293 chemicals were related to endocrine disruption, and nearly two-thirds of the products contained more than one of these chemicals. Cleaning products, synthetic detergents, fabric softeners, air fresheners, and deodorants have several hotspots for fragrances, isothiazolinones, glycol ethers, and parabens. The three most prevalent EDCs in household chemical products were added to act as fragrances and preservatives. The present study demonstrated that commonly occurring chemical combinations can be derived using an association rule mining algorithm. The results of this study will be useful in prioritizing chemical combinations and developing management plans for EDC mixture in consumer products.
Article
Isothiazolinone preservatives are known to cause contact dermatitis. Although they are used in household deodorizers and air fresheners, the actual extent of their use remains unclear. In this study, we developed a method to simultaneously analyze five isothiazolinones (2-methyl-4-isothiazilin-3-one: MI, 5-choro-2-methyl-4-isothiazolin-3-one: CMI, benzisothiazolin-3-one: BIT, 2-n-octyl-4-isothiazolin-3-one: OIT, 4,5-dichloro-n-octyl-4-isothiazolin-3-one: 2Cl-OIT) in spray-type household deodorizers and air fresheners. The samples were analyzed through solid-phase extraction and liquid chromatography–tandem mass spectrometry. Three solid-phase extraction cartridges were examined, and good results were obtained for the OASIS HLB Plus LP cartridge. The recoveries and standard deviations for isothiazolinone preservatives extracted using this cartridge were 72–99 and 1.6–6.0%, respectively. In addition, the limit of detection and limit of quantification were as follow: 0.012 and 0.037 μg/mL for MI, 0.029 and 0.089 μg/mL for CMI, 0.032 and 0.098 μg/mL for BIT, 0.013 and 0.040 μg/mL for OIT, and 0.015 and 0.047 μg/mL for 2Cl-OIT. Among the 51 analyzed products, only 10 were detected with isothiazolinone compounds. MI and CMI were detected in five products at concentration levels of 0.31–22 and 0.77–95 μg/mL, respectively, while BIT was detected in the other five products at 2.7–101 μg/mL.
Article
Isothiazolinones, a family of biocides, are used as preservatives for their fungicidal, bactericidal, and algacidal properties. These compounds can be found in a wide range of consumer and building products, such as paints, varnishes, shampoos, and liquid detergents. A robust analytical UPLC-MS/MS method to identify and quantify seven isothiazolinones (MIT, CMI, BIT, MBIT, BBIT, OIT, and DCOIT) in consumer products and their emissions was developed and validated according to ISO/IEC 17025. The limits of detection (LODs) ranged from 0.14 μg L−1 (BIT) to 0.54 μg L−1 (CMI). The method was applied for the quantification of the seven isothiazolinones in four types of consumer products (i.e., cosmetics, air fresheners, cleaning products, and building products) and the indoor emissions from a paint. Matrix effects were observed for the shampoo (63–74%), the shower gel (67–84%), and the ceramic glass cleaner (53–57%). All isothiazolinones indicated by the manufacturer (i.e., MIT, CMI, BIT, OIT, and DCOIT) were detected in the products and successfully quantified by the UPLC-MS/MS method.Graphical abstract
Article
Background Preservatives are widely used in cosmetic, household and industrial products to prevent microbial growth and spoiling of the products. There has been a recent epidemic of contact allergy to methylisothiazolinone (MI). Objectives To establish emerging trends in preservative contact allergy as MI is replaced. Methods We performed a retrospective study on consecutively patch tested patients at our centre from January 2011 to December 2019. Results A total of 7846 consecutively patch tested patients were included who were patch tested between January 2011 and December 2019. The prevalence of allergy to MI fell from a peak of 9.39% in 2013 to 1.98% in 2019. MI/methylcloroisothiazolinone(MCI) followed a similar trend with a peak prevalence of 7.85% in 2014 and falling to 1.39% in 2018. The prevalence of contact allergy to benzisothiazolinone (BIT) has steadily increased in 2014 from 0.26% (CI 0.03–0.93) to 3.42% (CI 2.43–4.66) in 2019. Conclusions Our data shows a significant increase in the prevalence of contact allergy to BIT over the last 6 years probably as a consequence of increased use in household products. It is essential to continue to look for emerging trends in contact allergy to enable prompt preventative measures to be taken. This article is protected by copyright. All rights reserved.
Article
Background: Sensitization to methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) is a worldwide problem. Washing machine detergents are suspected to cause cutaneous symptoms in highly sensitized patients. Little is known about the persistence of isothiazolinones in clothes that have been washed. Objective: The aim of the study was to analyze the possible persistence of MI, MCI, benzisothiazolinone, and octylisothiazolinone in common fabrics after machine washing. Methods: Different clothes (cotton, polyester, linen, and wool) were collected, and 4 types of wash were done (control, standard, standard + conditioner, and standard + double rinse). The samples were analyzed using ultrahigh-performance liquid chromatography. Results: The results showed that the concentrations of isothiazolinones were very low, independent of the type of material or wash. The highest levels were found in the control wash (hand wash), reaching a maximum of 0.4 ppm in the linen. Conclusions: Our findings suggest that it is not necessary to recommend that patients sensitized to MI avoid isothiazolinones in machine detergents or fabric conditioners or to double rinse. However, after using the detergent for hand washing (the control in our study), there may remain sufficient concentrations of isothiazolinones in clothes to produce symptoms in highly sensitized patients.
Article
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Methylisothiazolinone (MI) is a preservative commonly used in paints, detergents and cosmetics. It has been found to be a potent sensitizer. During the recent years there has been an epidemic increase in allergic contact dermatitis caused by MI (1). We present the case of a worker in the detergent production industry who developed severe allergic contact dermatitis following occupational exposure to MI, illustrating the need for attention to occupational exposure to MI in the production setting, where high concentrations of MI are used.
Article
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Background European legislation has banned the preservative methylisothiazolinone (MI) from inclusion in leave-on cosmetics. However, the risk for allergic reactions depends on exposure. The aim of this study was to determine the risk of MI in laundry detergents for household machine washing. Methods Different formulations of laundry detergents with commercial MI levels, up to one thousand ppm were used and three different types of clothes were washed in a normal household machine setting one time and 10 times. The level of MI was measured by HPLC. Results While MI could be retrieved in the positive control of clothes drenched with washing powder but not washed afterwards, MI could not be detected in any specimen of clothes washed under household conditions. The detection limit was 0.5 ppm. Conclusion It is important to discuss the difference of risk and hazard. While MI clearly is a high hazard as a strong contact allergen, the risk depends on exposure. Regarding the risk of exposure levels for the consumer to MI in clothes it can be stated that the use of MI in laundry detergents is safe for the consumer if these products are used according to the instructions in the normal household setting machine wash.
Article
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The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Article
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The chemical Kathon CG ® , a mixture of the preservatives methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI), was the leading cause of a worldwide epidemic of contact-allergic reactions in the eighties. From 2000 on, MI alone became allowed in industrial products and in 2005 authorities gave a green light for its use in leave-on and rinse-off cosmetics up to a maximum concentration of 100 ppm (0.01%). Following initial occupational cases, a continuously increasing number of consumers sensitized to MI have been reported and both Belgian and French allergy groups decided to routinely test MI in their baseline series from 2010 onwards. Two multicenter studies, comprising 8,680 and 7,874 patients in Belgium and France respectively, both clearly show the rise in contact allergy caused by MI, with a spectacular sensitization rate of ∼ 6.0% in 2012, even increasing to 7.0% in 2013. Mostly middle-aged women, presenting with facial-and/or hand dermatitis, were affected, although very young children were reported as well. Furthermore, the data confirmed that sensitization is primarily caused by cosmetics (mostly leave-on, but also rinse-off), household detergents and water-based paint. This unprecedented outbreak of contact sensitization to a preservative agent in Europe, and beyond, should have alerted the authorities much sooner and meanwhile the need for safer use concentrations of MI in cosmetics, detergents and industrial products is becoming more urgent every day.
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In this work, the development of a new efficient methodology applying, for the first time, matrix solid phase dispersion (MSPD) for the determination of sensitizer isothiazolinone biocides in cosmetics and household products - 2-methyl-3-isothiazolinone (MI), 5-chloro-2-methyl-3-isothiazolinone (CMI), 1,2-benzisothiazolinone (BzI) and 2-octyl-3-isothiazolinone (OI) - is described. The main factors affecting the MSPD extraction procedure, the dispersive phase and the elution solvent, are assessed and optimized through a multicategorical experimental design, using a real cosmetic sample. The most suitable extraction conditions comprise the use of 2g of florisil as dispersive phase and 5mL of methanol as elution solvent. Subsequently, the extract is readily analyzed by HPLC-MS/MS without any further clean-up or concentration steps. Method performance was evaluated demonstrating to have a broad linear range (R(2)>0.9980) and limits of detection (LOD) and quantification (LOQ) at the low nanogram per gram level, which are well below the required limits for UE regulation compliance. Satisfactory recoveries above 80%, except for MI (mean values close to 60%), were obtained. In all cases, the method precision (% RSD) was lower than 7%, making this low cost extraction method reliable for routine control. The validated methodology was finally applied to the analysis of a wide variety of cosmetics and household products. Most of the real samples analyzed have been shown to comply with the current European Cosmetic Regulation, although the results obtained for some rinse-off cosmetics (e.g. baby care products) revealed high isothiazolinone content.
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Products containing biocides are used for a variety of purposes in the home environment. To assess potential health risks, data on products containing biocides were gathered by means of a market survey, exposures were estimated using a worst case scenario approach (screening), the hazard of the active components were evaluated, and a preliminary risk assessment was conducted. Information on biocide-containing products was collected by on-site research, by an internet inquiry as well as research into databases and lists of active substances. Twenty active substances were selected for detailed investigation. The products containing these substances were subsequently classified by range of application; typical concentrations were derived. Potential exposures were then estimated using a worst case scenario approach according to the European Commission's Technical Guidance Document on Risk Assessment. Relevant combinations of scenarios and active substances were identified. The toxicological data for these substances were compiled in substance dossiers. For estimating risks, the margins of exposure (MOEs) were determined. Numerous consumer products were found to contain biocides. However, it appeared that only a limited number of biocidal active substances or groups of biocidal active substances were being used. The lowest MOEs for dermal exposure or exposure by inhalation were obtained for the following scenarios and biocides: indoor pest control using sprays, stickers or evaporators (chlorpyrifos, dichlorvos) and spraying of disinfectants as well as cleaning of surfaces with concentrates (hydrogen peroxide, formaldehyde, glutardialdehyde). The risk from aggregate exposure to individual biocides via different exposure scenarios was higher than the highest single exposure on average by a factor of three. From the 20 biocides assessed 10 had skin-sensitizing properties. The biocides isothiazolinone (mixture of 5-chloro-2-methyl-2H-isothiazolin-3-one and 2-methyl-2H-isothiazolin-3-one, CMI/MI), glutardialdehyde, formaldehyde and chloroacetamide may be present in household products in concentrations which have induced sensitization in experimental studies. Exposure to biocides from household products may contribute to induction of sensitization in the population. The use of biocides in consumer products should be carefully evaluated. Detailed risk assessments will become available within the framework of the EU Biocides Directive.
Article
1,2‐benzisothiazolin‐3‐one (BIT) is an antimicrobial agent wildly used as a preservative in non‐cosmetic products¹. It is a recognized allergen since 1976², responsible for occupational contact dermatitis in workers involved in the manufacturing of paints, plastic emulsions, air fresheners, textile and paper dyes, water softeners, pottery moulds, metallurgy and carpet industries³ This article is protected by copyright. All rights reserved.
Article
Consumers regularly use household care and personal care products (HC&PCPs). Isothiazolinones are included in HC&PCPs as preservatives and are being held responsible for an epidemic rise in allergic contact dermatitis (ACD). The objective of this study was to assess the origin and extent of dermal exposure in order to evaluate the risk of ACD from isothiazolinones in HC&PCP. Individual-based aggregate dermal exposure to four isothiazolinones was estimated using the newly proposed Probabilistic Aggregated Consumer Exposure Model–Kinetic, Dermal (PACEM-KD) by combining the reported individual use patterns for HC&PCP in Switzerland (N = 669 (558 adults), ages 0–91) with isothiazolinone concentrations measured in products used by the individual person. PACEM-KD extends the original PACEM by considering exposure duration, product dilution and skin permeability. PACEM-KD-based higher-tier exposure on palms (99th percentile) was 15.4 ng/cm², 1.3 ng/cm², 0.9 ng/cm², and 0.08 ng/cm² for the isothiazolinones 1,2‑Benzisothiazol‑3‑(2H)‑one (BIT), 2‑Octyl‑3(2H)‑isothiazolinone (OIT), 2‑Methylisothiazolin‑3(2H)‑one (MI), and 5‑Chloro‑2‑methyl‑4‑isothiazolin‑3‑one (CMI), respectively. Major sources of exposure to BIT included all-purpose cleaners, dishwashing detergent, and kitchen cleaner, while exposure to OIT mainly stems from a fungicide. For MI, the main contributors were dishwashing detergent and all-purpose wet wipes, and for CMI all-purpose cleaner. A Quantitative Risk Assessment (QRA) for BIT using Sensitization Assessment Factors (SAFs) indicates that around 1% of the Swiss population is at risk to be sensitized by BIT in cosmetics and household chemicals. For isothiazolinones in general the presented higher-tier modelling approach suggests that household cleaners are currently more important sources of exposure than cosmetics.
Article
Background: Sensitivity to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) has increased rapidly over recent years. This increase is mainly related to the extensive use of high concentrations of MI in cosmetic products, although a growing number of cases of occupational allergic contact dermatitis are caused by MCI/MI. Objective: The aim of this study was to examine the association between the increase in MCI/MI sensitization and the work undertaken by the patients in our area. Methods: A retrospective study was undertaken of the records of a total of 1179 patients who had undergone contact skin patch tests for MCI/MI from January 2005 to December 2015. A multivariate logistic regression analysis was performed to identify the factors independently associated with sensitivity to MCI/MI. Results: A constant increase in MCI/MI sensitization was observed over the observation period. The only work associated with a significant increase in the prevalence of MCI/MI sensitization was cleaning, with 38.5% of the cleaning professionals with MCI/MI sensitization consulting for cosmetics-related dermatitis. Conclusions: Occupational sensitization to MCI/MI in cleaning professionals is worryingly increasing. This, in turn, could possibly account for many cases of cosmetics-associated contact dermatitis. Our findings suggest that a review of the regulations with regard to isothiazolinone concentrations in industrial and household detergents is necessary.
Article
The isothiazolinone derivatives, methylchloroisothiazolinone (MCI), methylisothiazolinone (MI), benzisothiazolinone (BIT), and octylisothiazolinone (OIT), owing to their strong bactericide, fungicide and algicide properties, are widely used in non-cosmetic products, such as chemical (industrial) products, household detergents, and water-based paints, and the former two derivatives are also used in cosmetic products. However, given their inherent sensitization potential (with MCI > MI > BIT > OIT), allergic contact dermatitis is frequently observed, both in consumers as well as workers in various industries. In this review, we provide an update on the use of MCI/MI and MI in cosmetics, highlighting certain aspects of MI; the use of excessive concentrations, the presence in some less familiar cosmetic products, and the association with unusual clinical manifestations. Furthermore, the use of isothiazolinones in dish-washing and washing-machine liquids, cleaning agents for dental care, and their general presence in multi-purpose household detergents, which may elicit (airborne) allergic contact dermatitis, is discussed. Finally, we provide a brief overview of the use of isothiazolinone derivatives in the paint and textile industry, and of OIT in the leather industry in particular.
Article
Background. In recent years, the frequency of contact allergy to isothiazolinones has increased alarmingly in Europe, but only limited data are available on concentrations of isothiazolinones in consumer products. Objectives. To examine the current frequency of isothiazolinones [methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), benzisothiazolinone (BIT), and octylisothiazolinone (OIT)] in a wide array of detergents and cosmetics relevant for the Swiss population. Methods. By means of a market survey, the occurrence of isothiazolinones was investigated in 1948 consumer products. Of these, 88 products were analysed by liquid chromatography–high-resolution mass spectrometry after ultrasonic extraction. Results. Only 7.6% of all cosmetics contained isothiazolinones, but the prevalence in detergents was much higher (42.9%). The measured concentration ranges in detergents were 4.3–10, 3.5–279, 3.8–186 and 7.9 ppm (one product only) for MI, MCI, BIT, and OIT, respectively. For cosmetics, these were 1.3–133 and 4.8 ppm (one product only) for MI and MCI, respectively. Conclusions. Our study has shown that high concentrations of isothiazolinones (including MI) can be found in a large variety of products, in particular in detergents. Therefore, the safe use of these preservatives should be re-evaluated by including detergents in the exposure assessment.
Article
Herbal products have been widely used due to good antimicrobial, fragrance and medical properties. Essential oils and fragrances can be applied on the textile substrates as micro/nanocapsules to prolong lifetime by controlling the release rate. The present review tries to give a general overview on the application of micro/nanoencapsulated essential oils on the textile substrates to achieve aromatherapy textiles. These are divided into four diverse categories as the following: antimicrobial, perfumed, mosquito-repellent and medical textiles. The reports in this field revealed that the encapsulation technique plays an important role in the finishing of plant extracts on the textile substrates. It is also anticipated that aromatherapy textiles have to be developed in the new fields such as multifunctional textiles having wound-healing, antimicrobial and fragrant properties.
Article
Background: Octylisothiazolinone (OIT) is used as an antifungal agent by the leather industry. Objectives: To show sensitization to OIT from leather, and to highlight the potential implications when cross-reactivity between OIT and methylisothiazolinone (MI) is studied. Methods: Two patients with allergic contact dermatitis caused by a leather belt and shoes, respectively, were patch tested with methylchloroisothiazolinone (MCI)/MI, MI, MCI, OIT, and benzisothiazolinone (BIT). High-performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to detect isothiazolinone derivatives in leather goods. Additionally, files of OIT-sensitized patients, observed at the KU Leuven department during the period 1990-2015, were retrospectively analysed. Results: Both patients had been primarily sensitized to OIT, but the diagnosis in one of them could be achieved only when a higher patch test concentration of OIT (1000 ppm pet.) was used. HPLC-UV confirmed the presence of OIT in their leather goods. Non-relevant sensitization to MI was noted in both cases. Four additional cases of OIT sensitization from leather could be retrieved from the KU Leuven database. Conclusions: Non-occupational sensitization to OIT from leather may occur. Patch test concentrations of >250 ppm pet. may be necessary for diagnosis, and to show cross-reactivity with MI. Safer use limits for OIT in the leather industry may be needed.
Article
Background: In the light of the exceptionally high rates of contact allergy to the preservative methylisothiazolinone (MI), information about cross-reactivity between MI, octylisothiazolinone (OIT) and benzisothiazolinone (BIT) is needed. Objectives: To study cross-reactivity between MI and OIT, and between MI and BIT. Methods: Immune responses to MI, OIT and BIT were studied in vehicle and MI-sensitized female CBA mice by a modified local lymph node assay. The inflammatory response was measured by ear thickness, cell proliferation of CD4(+) and CD8(+) T cells, and CD19(+) B cells in the auricular draining lymph nodes. Results: MI induced significant, strong, concentration-dependent immune responses in the draining lymph nodes following a sensitization phase of three consecutive days. Groups of MI-sensitized mice were challenged on day 23 with 0·4% MI, 0·7% OIT and 1·9% BIT - concentrations corresponding to their individual EC3 values. No statistically significant difference in proliferation of CD4(+) and CD8(+) T cells was observed between mice challenged with MI compared with mice challenged with BIT and OIT. Conclusions: The data indicate cross-reactivity between MI, OIT and BIT, when the potency of the chemical was taken into account in choice of challenge concentration. This means that MI-sensitized individuals may react to OIT and BIT if exposed to sufficient concentrations.
Article
Methylisothiazolinone (MI) contact allergy is severely affecting consumers with allergic contact dermatitis, owing to its presence in cosmetics, household detergents, and water-based paints, in particular. Data on the true isothiazolinone concentrations in these products are scarce, and labelling may be incorrect. To report on the MI concentrations in such products marketed in Belgium, in order to verify the accuracy of labelling (when applicable) and compliance with EU regulations. Thirty cosmetics (18 leave-on and 12 rinse-off), eight detergents and four paints were analysed for MI by the use of high-performance liquid chromatography with ultraviolet detection. The analysed leave-on, and to a lesser extent the rinse-off, cosmetics, contained MI at concentrations far exceeding the permitted 100 ppm use concentration. Household detergents contained high concentrations of MI, and mislabelling occurred for both cosmetics and detergents. The (limited) data on paints are in line with the existing literature. Cosmetics and detergents may facilitate contact sensitization because of a (too) high MI concentration, and mislabelling may make its avoidance extremely difficult. Safer use concentrations and correct labelling should be ensured by adequate quality control. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Article
Isothiazolinone biocides are broad-spectrum preservatives that are widely used in cosmetics, household and industrial products. An increase in the number of cases of allergic contact dermatitis to isothiazolinone preservatives, namely, methylisothiazolinone and methylchloroisothiazolinone, have been recently noticed. The Food and Drug Administration relies on analytical methods to quantify levels of use of cosmetic ingredients and support enforcement action against products that are not in compliance with the law. In this study, an efficient ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of methylisothiazolinone and methylchloroisothiazolinone in selected cosmetic products. The lower limit of quantitation was determined to be 0.1 μg/g for both preservatives. A survey of 24 cosmetic products was conducted and found concentrations of methylisothiazolinone and methylchloroisothiazolinone ranging from not quantified, or below the lower limit of quantitation, to 89.64 μg/g and not quantified to 10.31 μg/g, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Article
The prevalence of contact allergy to the isothiazolinone preservative methylchloroisothiazolinone (MCI) in combination with methylisothiazolinone (MI) and MI alone has increased in the last couple of years. To investigate the prevalence of contact allergy to MI, MCI/MI and benzisothiazolinone (BIT) among patch tested patients at Gentofte Hospital, as well as the use of MI in cosmetic products. Patients patch tested with either MI, MCI/MI or BIT from 2010 to 2012 were included in the study. The MOAHLFA index was registered in all patch tested patients, and relevant exposures were determined in patients with an isothiazolinone allergy. In a market survey, the ingredient labels of cosmetic products were investigated for MI content. The prevalence of MI and MCI/MI contact allergy increased significantly from 2010 to 2012: from 2.0% to 3.7% for MI (n = 2766), and from 1.0% to 2.4% for MCI/MI (n = 2802). MI-allergic patients had occupational, hand and face dermatitis significantly more often, and were aged > 40 years. Cosmetics were the most common substances causing relevant exposure found in both MCI/MI-allergic and MI-allergic patients. MI was found in 3.3% of cosmetics on the Danish retail market. The increase in MI contact allergy is alarming, and urgent action is needed.