Cross-Reactivity Between Propylene Glycol and Butylene Glycol.

Background: Propylene glycol (PG) and butylene glycol (BG) are not known to be cross-reactors. However, no large-scale studies have assessed the cross-reactivity rate (CRR) between these 2 structurally and functionally similar compounds. Objectives: The aim of this study was to determine whether PG and BG demonstrate cross-reactivity. Methods: This is a retrospective chart review of 893 patients who underwent patch testing for both PG and BG from 2020 to 2022. The frequencies of positive reactions and concomitant reaction rates were calculated. Results: In our cohort, 53 (5.94%) patients reacted to PG and 13 patients (1.46%) reacted to BG. Of the patients who reacted to PG, 6 reacted to BG representing a CRR of 11.3%, whereas the CRR to PG in BG-allergic patients was 46.2%. Conclusions: For those allergic to BG, PG should be considered a cross-reactor. This relationship is somewhat unidirectional, as patients allergic to PG demonstrated a CRR to BG of only 11.3%, significantly lower than the 46.2% CRR to PG among BG-allergic patients.

Allergic contact dermatitis from propylene glycol: A case series from Australia.

BACKGROUND: Propylene glycol (PG) is used in a variety of cosmetics, food and pharmaceuticals. PG is a known sensitizer but also irritating when patch tested (PT). OBJECTIVES: The aims were to investigate the frequency of contact sensitization to PG and to identify cases of allergic contact dermatitis (ACD). METHODS: A retrospective study was performed on patients PT at the Skin Health Institute (SHI), Victoria, Australia to PG 5% pet. and PG 10% aq. between 1 January 2005 and 31 December 2020. RESULTS: In all, 6761 patients were PT to PG and 21 (0.31%) reacted. Of those 21 individuals, 9 (42.9%) had a relevant reaction. 75% of relevant positive reactions were in patients PT to PG 10% aq. The most common source of PG exposure was topical medicaments (77.8% of relevant reactions) and moisturizers, with the largest group being topical corticosteroids. CONCLUSION: Contact sensitization to PG in the patch test population remains uncommon, although it is possible that testing with concentrations of 5%-10% PG did not identify all reactions. Topical corticosteroids were the most important cause. Patients with suspected contact dermatitis to topical corticosteroids should be PT to PG.

Modulation of mucin secretion using combined polyethylene glycol-propylene glycol topical formulation in a hyperosmotic stress-based explant model.

Purpose: Ocular surface discomfort and dry eye disease are caused by a dysfunctional tear film. The efficacy of lubricating eye drops on the human eye is known, but the compositions may show differential effects on rescuing the tear film. Mucins form a critical layer of the tear film, a reduction of which may be causative for ocular surface conditions. Therefore, it is essential to develop relevant human-derived models to test mucin production. Methods: Human corneoscleral rims were obtained from a healthy donor (n = 8) post-corneal keratoplasty and cultured in DMEM/F12 media. Hyperosmolar stress mimicking dry eye disease was induced by exposing the corneoscleral rim tissues to +200 mOsml NaCl-containing media. The corneoscleral rims were treated with polyethylene glycol-propylene glycol (PEG-PG)-based topical formulation. Gene expression analysis was performed for NFAT5, MUC5AC, and MUC16. Secreted mucins were measured by enzyme-linked immunosorbent assay (ELISA) (Elabscience, Houston, TX, USA) for MUC5AC and MUC16. Results: The corneoscleral rims responded to hyperosmolar stress by upregulating NFAT5, a marker for increased osmolarity, as observed in the case of dry eye disease. The expression of MUC5AC and MUC16 was reduced upon an increase in hyperosmotic stress. The corneoscleral rim tissues showed induction of MUC5AC and MUC16 expression upon treatment with PEG-PG topical formulation but did not show significant changes in the presence of hyperosmolar treatments. Conclusion: Our findings showed that PEG-PG-based topical formulation slightly alleviated hyperosmolar stress-induced decrease in MUC5AC and MUC16 gene expression that is encountered in DED.

Pharmaceutical excipients with potential to cause adverse effects in paediatric nasal medicines.

Some pharmaceutical excipients may cause adverse reactions, excipient-related interactions and/or contraindications. Due to the unique characteristics of the paediatric population, adverse effects may occur to substances generally thought safe. The proportion of topical nasal medicines approved for paediatric use and the prevalence and labelling of excipients with known effect (EKE) in these products were compared in Serbia as a non-EU country and Croatia and Slovenia as EU countries. The study was designed as a post-authorization safety study and safety of excipients was considered in accordance with recommendations of the European Medicines Agency (EMA). More than 90% of topical nasal medicines registered in the three countries were approved for paediatric use and more than half of these paediatric medicines contained EKE that may cause adverse effects. Benzalkonium chloride was found in 52.38%, 55.81% and 59.09% of these products in Serbia, Croatia and Slovenia, respectively. Propylene glycol, benzyl alcohol, ethanol, methyl paraben, propyl paraben and boric acid were also present in a few analysed preparations. A significant number of EKE labelling deficiencies were detected in all three countries, hindering healthcare professionals' access to information needed for adequate patient counselling. A revision of the nasal paediatric medicines' PLs and SmPCs is recommended.

Formaldehyde in Electronic Cigarette Liquid (Aerosolized Liquid).

BACKGROUND: Aerosolized liquid (e-liquid) of electronic cigarettes can be toxic. Beyond the solvent (propylene glycol, vegetable glycerin) and nicotine, little is known about the liquid composition. Formaldehyde, a carcinogen and source of contact dermatitis, has been reported in the vaporized e-liquid, but no studies have assessed the actual e-liquid. OBJECTIVE: The aim of the study was to evaluate e-liquid products for the presence of formaldehyde. METHODS: Sixteen e-liquid products were purchased and analyzed for the release of formaldehyde using the chromotropic acid method of detection. RESULTS: Of the 16 e-liquids purchased, 4 (25%) were positive for the presence of formaldehyde; 2 were flavored and 2 were nonflavored. All positive e-liquids were in pods or disposable electronic cigarette devices, and 2 were purchased from local vape shops. The average nicotine content in the positive e-liquids was 3.85% versus 4.03% in the negative e-liquids. CONCLUSIONS: The e-liquid products contain toxic chemicals not declared on product labels, as shown in this study with 25.0% of e-liquids containing formaldehyde. All positive e-liquids were within pods or disposable devices. Continued analysis of e-liquids and increased product regulation are needed.

Contact Allergens in Prescription Topical Ophthalmic Medications.

BACKGROUND/OBJECTIVE: Both active and inactive ingredients in topical ophthalmic agents may cause allergic contact dermatitis. Here, we examined ingredients in prescription topical ophthalmic medications available in the United States. METHODS: A comprehensive list of topical ophthalmic medications was generated using AccessPharmacy. Categories included antiglaucoma, antibiotic, antibiotic/corticosteroid, corticosteroid, antiviral, antifungal, mydriatic, and miotic agents. For each formulation, ingredients were investigated using the National Institutes of Health US National Library of Medicine database and/or manufacturer websites. Counts and proportions were calculated for inactive ingredients, including those in the American Contact Dermatitis Society (ACDS) Core 90 Allergen Series. RESULTS: Two hundred sixty-four unique prescription ophthalmic medications met the inclusion criteria. The most common ACDS Core 90 allergen/cross-reactor inactive ingredient was benzalkonium chloride (68.1%, 180/264), followed by sorbates (11.7%, 31/264), parabens (6.8%, 18/264), sodium metabisulfite (3.8%, 10/264), propylene glycol (3.0%, 8/264), and lanolin (3.0%, 8/264). Approximately 21% (20.8%, 55/264) of products had no ACDS Core 90 allergens/cross-reactor inactive ingredients. The most common ACDS Core 90 allergen/cross-reactor active ingredients were aminoglycoside antibiotics, bacitracin/polymyxin B, and corticosteroids. Important non-ACDS Core 90 allergens included inactive ingredients, such as EDTA 28.0% and thimerosal 2.7%, as well as active ingredients, especially ß-blockers. CONCLUSIONS: Benzalkonium chloride, sodium metabisulfite, propylene glycol, and lanolin were common inactive ingredient allergens. Most ophthalmic categories had low allergen formulations available for patients with contact allergy.

The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent.

Vaping has become increasingly popular over the past decade. This pragmatic review presents the published biological effects of electronic cigarette vapour inhalation with a focus on the pulmonary effects. Special attention has been devoted to providing the documented effects specific to each major ingredient, namely propylene glycol/glycerol, nicotine and flavouring agents. For each ingredient, findings are divided according to the methodology used, being in vitro studies, animal studies and clinical studies. Finally, we provide thoughts and insights on the current state of understanding of the pulmonary effects of vaping, as well as novel research avenues and methodologies.

Possible effects of excipients used in the parenteral drugs administered in critically ill adults, children, and neonates.

BACKGROUND: Critically ill patients receiving parenteral drugs are at an increased risk of exposure to various excipients administered simultaneously and at increased amounts. Hence, we carried out the present study. RESEARCH DESIGN AND METHODS: Patients admitted in the adult, pediatric, and neonatal intensive care units were recruited following their consent. Details on their demographics, diagnoses, and drugs administered and the excipients were collected. RESULTS: Almost all the critically ill patients received drugs containing at least one excipient. Significant numbers of critically ill neonates received at least one of either known to be harmful or potentially harmful excipients. Critically ill neonates had significantly greater daily exposure of macrogol than children and adults; and benzyl alcohol (v/v) and propyl paraben compared to adults. Critically ill neonates and children had greater exposure to benzyl alcohol (w/v), methyl paraben, sodium metabisulfite than adults did. Benzyl alcohol exposure was likely to be several-fold high in critically ill patients. Exposures to benzyl alcohol and propylene glycol were possibly linked to increased risk of mortality particularly in neonates. CONCLUSION: Critically ill neonates and children are likely to receive a significantly greater quantity of harmful excipients than critically ill adults. Benzyl alcohol and propylene glycol exposure are likely to be associated with increased risk of mortality in critically ill.

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols.

BACKGROUND: In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE: The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS: Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n=8-10 per group) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16mg/mL nicotine (+Nic). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. RESULTS: Adult offspring of both sexes exposed to +Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNγ) in the diencephalon, as well as lower levels of hippocampal IFNγ (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. DISCUSSION: These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.

Patch Testing Results From the Massachusetts General Hospital Contact Dermatitis Clinic, 2007-2016.

BACKGROUND: Patch testing is the criterion standard for diagnosis of allergic contact dermatitis (ACD). OBJECTIVE: The aim of the study was to report the trends of patch testing results with the standard series at Massachusetts General Hospital from January 1, 2007, to December 31, 2016, compared with previous data from 1998 to 2006 and from 1990 to 2006 and those reported by the North American Contact Dermatitis Group. METHODS: Data were collected and analyzed from retrospective chart reviews, focusing on 50 allergens in our standard series. RESULTS: A total of 2373 patients were patch tested. One or more positive reactions were observed in 1428 patients (60.2%), and 1153 patients (48.6%) had a final primary diagnosis of ACD. Top 5 allergens were nickel (19.8%), fragrance mix I (14.6%), Myroxylon pereirae (balsam of Peru) (13.5%), neomycin (9.4%), and bacitracin (7.7%). Sensitization frequencies statistically increased over time for 3 allergens: nickel, neomycin, and propylene glycol, and decreased for 5 allergens: formaldehyde, paraben mix, thiuram mix, n-isopropyl-N-phenyl-4-phenylenediamine, and epoxy resin (P ≤ 0.001). CONCLUSIONS: Surveillance of ACD trends is essential to detect emerging sensitizers. Patch testing is an important diagnostic tool for detection of ACD to commonly encountered and potential allergens.

Alcohol-Related Dermatitis: A Review.

: Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Iatrogenic Propylene Glycol Intoxication Due to High-Dose Pentobarbital for Refractory Intracranial Hypertension: A Case Report.

Propylene glycol is a rarely reported toxicity from high-dose administration of certain intravenous drugs, including lorazepam and pentobarbital. We present a case of iatrogenic propylene glycol toxicity secondary to a high-dose pentobarbital infusion for the treatment of refractory intracranial hypertension due to cerebral venous sinus thrombosis. The patient developed metabolic acidosis and acute kidney failure secondary to propylene glycol toxicity. After initiation of continuous renal replacement therapy, the patient's acute renal failure and lactic acidosis resolved. Using the Naranjo scale, this case received a score of 5, defining it as a "probable" adverse drug event. In patients who develop lactic acidosis and acute renal failure after initiation of high-dose pentobarbital, propylene glycol toxicity should be higher up in the differential diagnosis. Monitoring the serum osmolality while on pentobarbital could help provide valuable information to prevent iatrogenic propylene glycol toxicity.

Allergic contact dermatitis to Tinosorb S, Scutellaria baicalensis, and other emerging allergens in cosmetics.

Patch tests are highly recommended in eczema patients with eyelid involvement. Sunscreen constitutes a potential cause of eyelid or facial allergic contact dermatitis, and should be considered in patients with refractory eczema on these locations. We report a patient sensitized to several emerging allergens such as bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), Scutellaria baicalensis extract, and propylene glycol with an eyelid dermatitis. Patch tests to the combined ingredients propylene carbonate, cyclopentasiloxane, and disteardimonium hectorite; and talc, Cl 77 491, and dimethicone/methicone copolymer were also positive. We highlight the importance of systematically patch testing with the cosmetics brought in by our patients, as well as with the individual ingredients whenever positive. The identification of emerging allergies to new compounds in cosmetics mainly depends on this practice.

Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary PG. Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, miRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL8, IL13, and TNFα), although the absolute magnitude of changes was small. There were no significant changes in mRNA or miRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.

Allergic Contact Dermatitis to Operating Room Scrubs and Disinfectants.

BACKGROUND: Both surgical personnel and patients undergoing procedures are exposed regularly to different antiseptic chemicals in various forms. Little is known about the ingredients in these antiseptics and the risk these products may provoke allergic contact dermatitis. OBJECTIVE: The aim of the study was to identify and characterize common allergens in surgical scrubs and patient surgical cleansers that health care workers and surgical patients may encounter in the perioperative period. METHODS: DailyMed website was searched using numerous terms for surgical disinfectants. Products used for health care worker handwashing/scrubbing or patient surgical cleansing/disinfecting were included. Each product's ingredients were recorded; those found on the 2017 American Contact Dermatitis Society (ACDS) Core Allergen Series were noted from each product. CONCLUSIONS: A total of 1940 products were identified, of which 267 were included in the analysis. A total of 66.3% contained iodine, 25.8% contained chlorhexidine digluconate, and 2.6% contained chloroxylenol. Within the group analyzed, 1586 ingredients were identified. Of these, 241 were ACDS Core Series allergens. Most products contained a single ACDS allergen. There were significant differences in allergens based on product type and active ingredient, with iodine-containing products having the fewest number of allergens. The most common ACDS allergens found were cocamide diethanolamide (22.5%), fragrance (21.7%), lanolin (19.5%), propylene glycol (6.7%), alkyl glucosides (6.0%), and sorbic acid derivatives (5.6%).

E-Cigarette Chemistry and Analytical Detection.

The study of e-cigarette aerosol properties can inform public health while longer-term epidemiological investigations are ongoing. The determination of aerosol levels of known toxins, as well as of molecules with unknown inhalation toxicity profiles, affords specific information for estimating the risks of e-cigarettes and for uncovering areas that should be prioritized for further investigation.

Toxicity tests of cryoprotecting agents for Mytilus galloprovincialis (Lamark, 1819) early developmental stages.

Global aquaculture production of blue mussel has increased over last years. This work reaffirms the great potential of cryopreservation technique on mussel industry and overcome economic barriers a cause of a traditional and rudimentary management and continue growing. The aim of this work is to set some preliminary basis attending to toxicity of cryoprotecting agents (CPAs) on different development stages of Mytilus galloprovincialis as a start point to develop a stable cryopreservation protocol. Toxicity tests were carried out by using common CPAs (dimethyl-sulfoxide (Me2SO), glycerol, (GLY), propylene glycol (PG) and ethylene glycol (EG)) in a range from 0.5 to 3 M on fertilized egg, trochophore larva, and D-larva of Mytilus galloprovincialis. Results evidenced more resistance of older development stages to toxicity. Of all CPAs tested, toxicity testing highlights PG or EG as suitable CPAs for cryopreservation of early development stages; whereas D-larva was unaffected by any of the CPAs tested. Preliminary cryopreservation trials were developed to obtain information into cell cryoprotection. Further research should be focused on membrane permeability and other parameters, such as the balance between toxicity and cryoprotective effect of CPAs.