Is benzyl alcohol a significant contact sensitizer?

BACKGROUND: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. OBJECTIVES: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. PATIENTS AND METHODS: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. RESULTS: Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol-positive patients, compared to benzyl alcohol-negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. CONCLUSIONS: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful.

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.

Excipient exposure in very low birth weight preterm neonates.

OBJECTIVE: The excipients benzyl alcohol, propylene glycol and ethanol are present in medications used in the neonatal intensive care unit. Exposure to high levels can have adverse effects in a neonatal population. The objective was to quantify excipient exposure in very low birth weight (VLBW) neonates and identify risk factors associated with greater exposure. STUDY DESIGN: A retrospective record review of VLBW infants admitted over 1 year. Excipient exposures were calculated and multivariable regression analyses identified risk factors for increasing exposure. RESULTS: In total, 98% of subjects were exposed to at least one excipient. A total of 5 to 9% received doses higher than recommended for adults. Necrotizing enterocolitis, seizure, bronchopulmonary dysplasia and longer stay predicted higher excipient exposure. CONCLUSION: The excipients examined are in medications commonly prescribed for VLBW neonates, and cumulative doses may exceed recommended exposures for adults. Although safety profiles have not been established, judicious use of medication containing these excipients is warranted for this population.

Benzyl alcohol protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes but causes mitochondrial dysfunction and cell death at higher doses.

Acetaminophen (APAP) hepatotoxicity is a serious public health problem in western countries. Current treatment options for APAP poisoning are limited and novel therapeutic intervention strategies are needed. A recent publication suggested that benzyl alcohol (BA) protects against APAP hepatotoxicity and could serve as a promising antidote for APAP poisoning. To assess the protective mechanisms of BA, C56Bl/6J mice were treated with 400 mg/kg APAP and/or 270 mg/kg BA. APAP alone caused extensive liver injury at 6 h and 24 h post-APAP. This injury was attenuated by BA co-treatment. Assessment of protein adduct formation demonstrated that BA inhibits APAP metabolic activation. In support of this, in vitro experiments also showed that BA dose-dependently inhibits cytochrome P450 activities. Correlating with the hepatoprotection of BA, APAP-induced oxidant stress and mitochondrial dysfunction were reduced. Similar results were obtained in primary mouse hepatocytes. Interestingly, BA alone caused mitochondrial membrane potential loss and cell toxicity at high doses, and its protective effect could not be reproduced in primary human hepatocytes (PHH). We conclude that BA protects against APAP hepatotoxicity mainly by inhibiting cytochrome P450 enzymes in mice. Considering its toxic effect and the loss of protection in PHH, BA is not a clinically useful treatment option for APAP overdose patient.

Postprocedural pain in shoulder arthrography: differences between using preservative-free normal saline and normal saline with benzyl alcohol as an intraarticular contrast diluent.

OBJECTIVE: The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. SUBJECTS AND METHODS: From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. RESULTS: Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends over time were highly significant (p < 0.0001). CONCLUSION: Shoulder arthrography is often associated with postprocedural discomfort that begins immediately after the procedure and resolves by 48 hours. There is significantly increased patient discomfort at 6 and 48 hours when using normal saline preserved with benzyl alcohol as a diluent compared with using normal saline without preservative as a diluent.

Effects of Litchi chinensis fruit isolates on prostaglandin E(2) and nitric oxide production in J774 murine macrophage cells.

BACKGROUND: Litchi chinensis is regarded as one of the 'heating' fruits in China, which causes serious inflammation symptoms to people. METHODS: In the current study, the effects of isolates of litchi on prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production in J774 murine macrophage cells were investigated. RESULTS: The AcOEt extract (EAE) of litchi was found effective on stimulating PGE(2) production, and three compounds, benzyl alcohol, hydrobenzoin and 5-hydroxymethyl-2-furfurolaldehyde (5-HMF), were isolated and identified from the EAE. Benzyl alcohol caused markedly increase in PGE(2) and NO production, compared with lipopolysaccharide (LPS) as positive control, and in a dose-dependent manner. Hydrobenzoin and 5-HMF were found in litchi for the first time, and both of them stimulated PGE(2) and NO production moderately in a dose-dependent manner. Besides, regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA expression and NF-κB (p50) activation might be involved in mechanism of the stimulative process. CONCLUSION: The study showed, some short molecular compounds in litchi play inflammatory effects on human.

The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis).

Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

[The usage of synthol in the body building]. / Stosowanie syntholu w kulturystyce.

Synthol consists usually of oil, benzyl alcohol and lidocain. It consists of 85% of oil (normally it is oil built by medium-length MTC chains because it gives the best effects), 7,5% of lidocain (painkiller), 7,5% of alcohol (to sterilize the mixture). Synthol is a substance used by body builders as a temporary implant which is injected deeply into the muscle. The enlargement effects are immediate. Synthol is used in small groups of muscles to enlarge their volume (for example triceps, biceps, deltoids, muscles of the calf). Some serious drawbacks can be visible while using synthol. The muscles deform and become unnaturally shaped. The side effects of synthol are manifold and they can also cause a damage of nerves, oil embolic of the pulmonary, occlusion of the pulmonary artery, myocardial infarction, cerebral stroke and infectious complications.

PM101: a cyclodextrin-based intravenous formulation of amiodarone devoid of adverse hemodynamic effects.

Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.

Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates.

OBJECTIVE: To document neonatal exposures to the potentially harmful pharmaceutical excipients benzyl alcohol (BA) and propylene glycol (PG) present in parenteral medications routinely administered in the intensive care unit. DESIGN: Retrospective, observational study. SETTING: Neonatal and pediatric intensive care units of a tertiary care, university hospital. PATIENTS: Randomly selected sample of 170 episodes of exposure to parenteral medications containing BA (n = 88) or PG (n = 82). MEASUREMENTS: We identified all medication sources of BA or PG administered to study neonates during hospitalization, and calculated cumulative doses (mg/kg/day and mg/day) of BA or PG received as a result of exposure to those medications. MAIN RESULTS: We observed a wide range in the cumulative excipient dose received by neonates. Median (range) cumulative dose was 4.5 mg/kg/day (0.6-319.5 mg/kg/day) for BA, and 204.9 mg/kg/day (17.3-9472.7 mg/kg/day) for PG. Patients who received medications via continuous infusion received significantly higher excipient doses than patients who received medications intermittently (p < 0.0001). In this subset of patients, median cumulative excipient doses (BA, 106.3 mg/kg/day and PG, 4554.5 mg/kg/day) were approximately 21 and 180 times the acceptable daily intakes of BA and PG (5 and 25 mg/kg/day), respectively, and exceeded the doses above which toxicity has been reported in infants. No significant correlation between duration of medication administration and cumulative excipient exposure was identified for BA or PG. Midazolam and lorazepam were involved in over two-thirds of BA and PG exposures, respectively. CONCLUSIONS: Critically ill neonates, especially those receiving medications by continuous infusion, are at risk of being exposed to BA and PG at potentially toxic doses during routine medication administration. Given the serious adverse reactions known to be associated with BA and PG, future studies are warranted to determine the clinical consequences associated with this degree of excipient exposure.

Elevation of intraocular pressure after intravitreal injection of triamcinolone acetonide in Taiwanese patients.

The purpose of this study was to investigate the incidence and timing of elevation in intraocular pressure (IOP) after intravitreal injection of triamcinolone acetonide (IVTA). This was a retrospective observational case series that included 52 eyes from 52 patients. All patients received intravitreal injection with 4 mg of triamcinolone acetonide. Significant IOP elevation was defined as pressure greater than 21 mmHg. There were 26 males and 26 females included in this study. The mean age was 59.4 years. The mean IOP at baseline and postoperative mean highest IOP were 14.6 mmHg and 21.5 mmHg, respectively. There were 19 (36.5%) patients who experienced significant IOP elevation at a mean of 26.0 days after IVTA. IOP was well-controlled by topical antiglaucoma medication in 17 of these 19 patients. IOP elevation after intravitreal injection with 4 mg of triamcinolone acetonide is not a rare finding. This phenomenon usually starts approximately 1 month after IVTA. Patients considering this treatment should be fully informed of this known adverse effect.