sodium-benzoate and Urticaria

Benzyl Alcohol is an aromatic alcohol used in a wide variety of cosmetic formulations as a fragrance component, preservative, solvent, and viscosity-decreasing agent. Benzoic Acid is an aromatic acid used in a wide variety of cosmetics as a pH adjuster and preservative. Sodium Benzoate is the sodium salt of Benzoic Acid used as a preservative, also in a wide range of cosmetic product types. Benzyl Alcohol is metabolized to Benzoic Acid, which reacts with glycine and excreted as hippuric acid in the human body. Acceptable daily intakes were established by the World Health Organization at 5 mg/kg for Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Benzoic Acid and Sodium Benzoate are generally recognized as safe in foods according to the U.S. Food and Drug Administration. No adverse effects of Benzyl Alcohol were seen in chronic exposure animal studies using rats and mice. Effects of Benzoic Acid and Sodium Benzoate in chronic exposure animal studies were limited to reduced feed intake and reduced growth. Some differences between control and Benzyl Alcohol-treated populations were noted in one reproductive toxicity study using mice, but these were limited to lower maternal body weights and decreased mean litter weights. Another study also noted that fetal weight was decreased compared to controls, but a third study showed no differences between control and Benzyl Alcohol-treated groups. Benzoic Acid was associated with an increased number of resorptions and malformations in hamsters, but there were no reproductive or developmental toxicty findings in studies using mice and rats exposed to Sodium Benzoate, and, likewise, Benzoic Acid was negative in two rat studies. Genotoxicity tests for these ingredients were mostly negative, but there were some assays that were positive. Carcinogenicity studies, however, were negative. Clinical data indicated that these ingredients can produce nonimmunologic contact urticaria and nonimmunologic immediate contact reactions, characterized by the appearance of wheals, erythema, and pruritus. In one study, 5% Benzyl Alcohol elicited a reaction, and in another study, 2% Benzoic Acid did likewise. Benzyl Alcohol, however, was not a sensitizer at 10%, nor was Benzoic Acid a sensitizer at 2%. Recognizing that the nonimmunologic reactions are strictly cutaneous, likely involving a cholinergic mechanism, it was concluded that these ingredients could be used safely at concentrations up to 5%, but that manufacturers should conside

Topics: Animals; Benzoic Acid; Benzyl Alcohol; Carcinogenicity Tests; Consumer Product Safety; Cosmetics; Dermatitis, Phototoxic; Humans; Inhalation Exposure; Lethal Dose 50; Muscle, Smooth; Mutagenicity Tests; Photosensitivity Disorders; Skin Diseases; Sodium Benzoate; Toxicity Tests, Acute; United States; United States Food and Drug Administration; Urticaria

In Europe amoxicillin plus clavulanic acid is the most commonly prescribed antibiotic and sodium benzoate is contained in the suspension formulation as a preservative.. We studied the relevance of sodium benzoate as the culprit agent. In a group of children with a history of adverse reactions to amoxicillin plus clavulanic acid suspension.. A total of 89 children were enrolled over a period of 3 years (2006 - 2009). Single blind oral provocation tests (OPTs) with amoxicillin plus clavulanic acid, sodium benzoate and placebo were performed. 20 children with recurrent idiopathic urticaria were investigated as a control group.. according to personal history: 70% of reactions were late in developing while 23% of reactions were immediate and for 5% of the cases it was not possible to define the timing. 8 children (8/89=9%) resulted positive to the provocation tests with amoxicillin plus clavulanic acid; ten children (10/89=11%) had positive results with sodium benzoate; 3% had a double positivity (i.e. excipient and active drug). The timing of reactions significantly differs between the Amoxicillin plus clavulanic acid and sodium benzoate groups (p=0.002).. Sodium benzoate probably acts through a non-immunologic mechanism and care should be given to children allergic to sodium benzoate containing pharmaceutical formulations.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Child; Child, Preschool; Drug Eruptions; Female; Humans; Male; Preservatives, Pharmaceutical; Recurrence; Single-Blind Method; Sodium Benzoate; Suspensions; Time Factors; Urticaria

Sodium benzoate (E 211) is widely used to delay yeast spoilage of acidic foods and beverages. Numerous cases of adverse reactions to benzoate have been recorded, but most of the studies that have been conducted lacked proper placebo controls or blinding.. The aim of this study is to determine the incidence of intolerance to sodium benzoate among subjects who experienced repeated episodes of acute urticaria/angio-oedema following the ingestion of a meal or a product containing this substance.. This was a retrospective study based on the analysis of data from patients reported to have experienced episodes of urticaria, with or without angio-oedema, after ingesting meals or products containing sodium benzoate. At the first visit to the outpatients clinic, a careful history was taken. Patients were then given the following diagnostic tests: tests for IgE for common inhalant allergens and food allergens, and a double-blind, placebo-controlled challenge with sodium benzoate.. A total of 47 subjects were enrolled in the study; five (11%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (2%) had a reaction after the ingestion of 75 mg of sodium benzoate without an adverse reaction to placebo.. This study shows that the percentage of repeated episodes of acute urticaria/angio-oedema reactions induced by sodium benzoate is very low (2%). In view of our results, we suggest that when faced with patients who have suffered adverse reactions that could be attributed to sodium benzoate, physicians should also carefully evaluate other possible causes.

Topics: Acute Disease; Adult; Angioedema; Double-Blind Method; Drug Eruptions; Female; Food Additives; Food Hypersensitivity; Humans; Immunoglobulin E; Male; Middle Aged; Retrospective Studies; Skin Tests; Sodium Benzoate; Urticaria

Topics: Administration, Oral; Child, Preschool; Dermatitis, Allergic Contact; Facial Dermatoses; Female; Humans; Sodium Benzoate; Urea Cycle Disorders, Inborn; Urticaria

The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU).. Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine.. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients.. Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Topics: Administration, Oral; Adult; Aspirin; Biomarkers; Bronchoconstrictor Agents; Chronic Disease; Controlled Clinical Trials as Topic; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Hypersensitivity; Female; Food Additives; Humans; Italy; Leukotriene E4; Male; Methylhistamines; Middle Aged; Sodium Benzoate; Sodium Glutamate; Sulfites; Tartrazine; Time Factors; Urticaria