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PubMedDate not supplied

The approach adopted in the UK for the estimation of the intake of food additives.

The UK has developed considerable experience in the estimating additive intake over the past 20 years. The earliest approach involved collecting large amounts of detailed information on additive concentrations and aimed to provide accurate estimates of intake for all additives in a given class. This has been replaced in recent times by a hierarchical approach which is applied to selected additives following an initial prioritization. Initial intake estimates are made using readily available data and conservative assumptions about additive occurrence and food consumption. More refined calculations are not necessary if the initial estimate shows that intake is well below the Acceptable Daily Intake. Once the level of intake has been established, it is only necessary to repeat the estimation if market information shows that there have been substantial changes in additive usage or food consumption. A similar approach is recommended for adoption across the European Union.

Food↗
PubMed1986

Cell-mediated immune responses to artificial food additives in chronic urticaria.

In some cases of chronic urticaria it is suspected that food additives such as tartrazine and sodium benzoate or salicylates may play a role in the pathogenesis of the condition. Since, at times, chronic urticaria may appear histologically similar to a mild cell-mediated immune response, the release of the T cell-derived lymphokine leucocyte inhibitory factor (LIF), in response to incubation with these additives and with acetylsalicylic acid (ASA), was measured in vitro using cells from normal controls, from patients with chronic urticaria with or without clinically associated additive sensitivity and from patients with asthma with or without associated ASA sensitivity. It was found that significant production of LIF occurred in response to tartrazine and sodium benzoate in those individuals with chronic additive induced urticaria. In addition, tartrazine caused LIF release from mononuclear cells of ASA-sensitive asthmatics. These results may indicate a possible role for additive-induced cell-mediated immune responses in the pathogenesis of some cases of chronic urticaria and suggest a potential diagnostic test for this condition.

Adolescent↗
PubMed1987

Hypersensitivity reactions to food additives.

Only seldom have food additives been shown to cause true allergic (immunological) reactions. Adverse effects due to various pharmacological or other mechanisms are much more common. The individual tolerance may be decreased for one reason or another, and may fluctuate from time to time. Many patients suffering from food additive reactions have atopic constitutions and such clinical symptoms as flexural dermatitis, rhinitis and asthma. The most important skin symptoms caused by food additives are urticaria, angioneurotic edema, and contact urticaria. Azo dyes, benzoic acid and several other common food additives may aggravate or, more rarely, even cause urticaria. Spices are one of the most common causes of immunological contact urticaria. Non-immunological contact urticaria is produced by numerous spices, benzoic acid, sorbic acid, cinnamic acid, and many essential oils. Asthma and rhinitis are the main hypersensitivity symptoms in the respiratory tract, and azo dyes, benzoic acid, and sulfitic food additives are the most common causative agents. Systemic and respiratory reactions to food colorants and benzoates have been claimed to occur more frequently in acetylsalicylic acid- (ASA-)sensitive patients than in non-reactors. Hypersensitivity reactions in organs other than the skin and respiratory tract are rare or poorly documented. Psychological factors play an essential role in both food and food additive reactions.

Dermatitis↗
PubMed1994

Adverse reactions to food additives in children with atopic symptoms.

In a multicenter study conducted at four Danish hospital pediatric departments, the parents of 472 consecutive children were informed of this project to determine the incidence of intolerance of food additives among children referred to an allergy clinic with symptoms of asthma, atopic dermatitis, rhinitis, or urticaria. After a 2-week period on an additive-free diet, the children were challenged with the eliminated additives. The food additives investigated were coloring agents, preservatives, citric acid, and flavoring agents. Carbonated "lemonade" containing the dissolved additives was used for the open challenge. Two doses were used: a low dose and a 10-fold higher dose. Gelatin capsules were used for a double-blind challenge. The children were 4-15 years old, and they were attending an outpatient pediatric clinic for the first time. Of the 379 patients who entered the study, 44 were excluded and 335 were subjected to open challenge. A total of 23 children developed positive reactions after the open challenge. Sixteen of these patients accepted the double-blind challenge, and six showed a positive reaction to preservatives (atopic dermatitis, asthma, rhinitis), coloring agents (atopic dermatitis, asthma, urticaria, gastrointestinal symptoms), and citric acid (atopic dermatitis, gastrointestinal symptoms). The incidence of intolerance of food additives was 2% (6/335), as based on the double-blind challenge, and 7% (23/335), as based on the open challenge with lemonade. Children with atopic skin symptoms had a statistically increased risk of a positive reaction. This may have consequences for the future clinical investigation of children with atopic cutaneous symptoms.

Adolescent↗
PubMed1991

Effects of additives and growth environment on preservation and digestibility of wheat silage fed to Holstein heifers.

Wheat grown in two separate years under different environmental conditions was fed as silage to investigate effects of additives on forage preservation and digestibility. Direct-cut wheat was harvested in an early head stage of maturity. Wheat was drought stressed in yr 1 and averaged 41.6% DM, and yr 2 averaged 23.0% DM at harvest. Forage was ensiled in 10 900-kg concrete stave silos; 2 per year were assigned to one of five treatments consisting of control, treatment with an enzyme-chemical product, or treatment with one of three different types of lactic acid bacterial inoculants. Each year, during two 12-d periods, forage from five different silos was fed individually for ad libitum intake, separate from concentrate (1.1% of BW) to 15 Holstein heifers (average BW 228 +/- 32 kg). Wheat forage and silage from yr 1 was lower in CP but higher in NDF, ADF, lignin, and starch than that harvested in yr 2. Silage additives decreased DM and NDF recovery in yr 1 and increased DM, NDF, and neutral detergent solubles recovery in yr 2. Additives increased the ratio of lactic to acetic acid and decreased ammonia in silage both years. Additives increased DM and fiber digestibilities of wheat silage-based rations fed to Holstein heifers in yr 2. In vitro digestibility indicated that these improvements were associated with a reduction in the lag phase of forage digestion. The rate of in vitro DM digestibility was positively correlated with silage DM recovery, suggesting an association with nutrient preservation. Wheat preservation and digestibility both were improved by silage additives when wheat was grown under normal environmental conditions, but losses were greater with additives in drought-stressed forage.

Animals↗
PubMed2004

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of food additives (including flavouring agents) and contaminants, assessments of intake, and the establishment and revision of specifications for food additives. A summary follows of the Committee's evaluations of toxicological and intake data on various specific food additives (alpha-amylase from Bacillus lichenformis containing a genetically engineered alpha-amylase gene from B. licheniformis, annatto extracts, curcumin, diacetyl and fatty acid esters of glycerol, D-tagatose, laccase from Myceliophthora thermophila expressed in Aspergillus oryzae, mixed xylanase, beta-glucanase enzyme preparation produced by a strain of Humicola insolens, neotame, polyvinyl alcohol, quillaia extracts and xylanase from Thermomyces lanuginosus expressed in Fusarium venenatum), flavouring agents, a nutritional source of iron (ferrous glycinate, processed with citric acid), a disinfectant for drinking-water (sodium dichloroisocyanurate) and contaminants (cadmium and methylmercury). Annexed to the report are tables summarizing the Committee's recommendations for ADIs of the food additives, recommendations on the flavouring agents considered, and tolerable intakes of the contaminants considered, changes in the status of specifications and further information requested or desired.

Animals↗
PubMed2005

Evaluation of certain food additives.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, with a view to recommending acceptable daily intakes (ADIs) and to prepare specifications for the identity and purity of food additives. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of food additives (including flavouring agents) and contaminants, assessments of intake, and the establishment and revision of specifications for food additives. A summary follows of the Committee's evaluations of toxicological and intake data on various specific food additives (benzoyl peroxide, alpha-cyclodextrin, hexose oxidase from Chondrus crispus expressed in Hansenula polymorpha, lutein from Tagetes erecta L., peroxyacid antimicrobial solutions containing 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP), steviol glycosides, D-tagatose, xylanases from Bacillus subtilis expressed in B. subtilis, zeaxanthin), flavouring agents, and a natural constituent (glycyrrhizinic acid). Annexed to the report are tables summarizing the Committee's recommendations for ADIs of the food additives, recommendations on the flavouring agents and natural constituent considered, changes in the status of specifications, and further information requested or desired.

Consumer Product Safety↗
PubMedDate not supplied

Testing of the palatability of Thymus vulgaris L. and Origanum vulgare L. as flavouring feed additive for weaner pigs on the basis of a choice experiment.

The objective of the study at hand was to investigate within the framework of a pilot project the preference of weaner pigs for either an ad libitum standard feed with thyme or oregano herb as flavouring additive or an ad libitum standard feed without any herbal additive. Thyme or oregano herbs or a combination of both were offered in two different concentrations each (1% and 0.1%) as additive (experimental diets) in standard diet in comparison to the latter without herbal additive (control diet) free of choice. The dosage of the two herbs in terms of total essential oil(s) in the feeds used in the study was 0.02% or 0.002% (v/w), which was equivalent to 1% or 0.1% herbs in the mixture, respectively. A Latin square according to Williams (1949) was used with 6 groups in order to record possible differences in feed intake. All experimental diets aside from that mixed with 0.1% thyme herb were, in comparison to the control diet, significantly less ingested. Where the weanling was given the choice, it did not choose feed with any flavouring additive. Further studies aimed at assessing the use of herbs as aroma additive in the form of a choice experiment are recommended.

Animal Feed↗
PubMedDate not supplied

[Incidence of adverse reactions to additives. Our experience over 10 years].

No published information exists about the incidence of food additives reactions in the general population. Most studies have been made in patients with urticaria and bronchial asthma. The majority of them lack an adequate design and, therefore, the reported results should be interpreted with extreme caution. In this article, we expose our ten years experience in this field. We have added up 1941 oral provocation tests, with an ample battery of additives, administering the tested substances directly or in aqueous or acid solution (1110 in patients with urticaria, mainly chronic urticaria, and 831 in asthmatic subjects, with or without aspirin intolerance). From these exhaustive data, we get the following conclusions: 1) in contrast with other-investigators, and using similar or even higher provocation doses, we get a very low incidence of adverse reactions. 2) We are sceptical that food additives play any role in chronic urticaria or in other cutaneous processes (only 0.63% provocation tests resulted in an urticarial exacerbation, and none of them was repeated after re-provocation). 3) In asthmatic patients, similar results were obtained, except with sulfites in acid solution challenge test (10% asthmatic exacerbations), possibly as a sign of nonspecific bronchial hyperreactivity. 4) The prescription of food additives free restrictive diets does not seem to be justified. The should be followed only by those patients with clear evidence of additives reactions. 5) In most cases, with punctual exceptions, the study of food additives reactions, in clinical allergy, implies a waste of time.

Adult↗
PubMed1983

Lithium carbonate addition in tricyclic antidepressant-resistant unipolar depression. Correlations with the neurobiologic actions of tricyclic antidepressant drugs and lithium ion on the serotonin system.

Preliminary reports suggested that the addition of lithium carbonate to the regimen of patients treated with, but not responding to, a tricyclic antidepressant (TCA) drug can induce a rapid alleviation of depression. We examined the effect of lithium carbonate addition in 39 patients with unipolar depression whose conditions were not improved by at least three weeks' TCA drug administration. In 30 of 42 observations, lithium carbonate brought about a greater than 50% improvement within 48 hours. In a second study, the effects of lithium carbonate addition were compared in five amitriptyline hydrochloride-pretreated and five placebo-pretreated patients who showed no improvement after a three-week treatment. All five patients receiving amitriptyline showed a greater than 50% improvement 48 hours after lithium carbonate addition, whereas only one patient in the placebo group showed a marked response. In a third study the effect of lithium carbonate withdrawal was studied in nine TCA-resistant patients who had shown a marked improvement 48 hours after lithium addition. Only five of these patients had a relapse five days after lithium discontinuation. Since animal studies have shown that TCA drugs sensitize forebrain neurons to serotonin and that lithium enhances the activity of serotonin-containing neurons, we propose that the antidepressant effect of lithium addition in TCA-resistant patients might be mediated by enhancing serotonin neurotransmission.

Adult↗
PubMed2005

Long-acting beta2-agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma.

BACKGROUND: Long-acting inhaled beta2-adrenergic agonists are recommended as 'add-on' medication to inhaled corticosteroids in the maintenance therapy of asthmatic adults and children aged two years and above. OBJECTIVES: To quantify in asthmatic patients the safety and efficacy of the addition of long-acting beta2-agonists to inhaled corticosteroids on the incidence of asthma exacerbations, pulmonary function and other measures of asthma control. SEARCH STRATEGY: We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers, until April 2004. SELECTION CRITERIA: RCTs were included that compared the addition of inhaled long-acting beta2-agonists to corticosteroids with inhaled corticosteroids alone for asthma therapy in children aged two years and above and in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptom scores, adverse events and withdrawal rates. MAIN RESULTS: Of 594 identified citations, 49 trials met the inclusion criteria: 27 full-text publications, one unpublished full-text report and 21 abstracts. Twenty-three citations (21 abstracts and two full-text publications) provided data in insufficient detail, 26 trials contributed to this systematic review. All but three trials were of high methodological quality. Most interventions (N = 26) were of four-month duration or less. Eight trials focused on children and 18 on adults, with participants generally symptomatic with moderate airway obstruction despite their current inhaled steroid regimen. If a trial had more than one intervention or control group, additional control to intervention comparisons were considered separately. Formoterol (N = 17) or salmeterol (N = 14) were most frequently added to low-dose inhaled corticosteroids (200 to 400 microg/day of beclomethasone (BDP) or equivalent). The addition of a daily long-acting beta2-agonist (LABA) reduced the risk of exacerbations requiring systemic steroids by 19% (relative risk (RR) 0.81, 95% CI 0.73 to 0.90). The number needed to treat for one extra patient to be free from exacerbation for one year was 18 (95% CI 13 to 33). The addition of LABA significantly improved FEV1 (weighted mean difference (WMD) 170 mL, 95% CI 110 to 240) using a random-effects model, increased the proportion of symptom-free days (WMD 17%, 95% CI 12 to 22, N = 6 trials) and rescue-free days (WMD 19%, 95% CI 12 to 26, N = 2 trials). The group treated with LABA plus inhaled corticosteroid showed a reduction in the use of rescue short-acting beta2-agonists (WMD -0.7 puffs/day, 95% CI -1.2 to -0.2), experienced less withdrawals due to poor asthma control (RR 0.5, 95% CI 0.4 to 0.7) and less withdrawals due to any reason (RR 0.9, 95% CI 0.8 to 0.98), using a random-effects model. There was no group difference in risk of overall adverse effects (RR 0.98, 95% CI 0.92 to 1.05), withdrawals due to adverse health events (RR 1.29, 95% CI 0.96 to 1.75) or specific adverse health events. AUTHORS' CONCLUSIONS: In patients who are symptomatic on low to high doses of inhaled corticosteroids, the addition of a long-acting beta2-agonist reduces the rate of exacerbations requiring systemic steroids, improves lung function, symptoms and use of rescue short-acting beta2-agonists. The similar number of serious adverse events and withdrawal rates in both groups provides some indirect evidence of the safety of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.

Administration, Inhalation↗
PubMed2005

Joint effect of selection, linkage and partial inbreeding on additive genetic variance in an infinite population.

Under the inifinitesimal model of gene effects, selection reduces the additive genetic variance by inducing negative linkage disequilibrium among selected genes. If the selected genes are linked, the decay of linkage disequilibrium is delayed, and the reduction of additive genetic variance is enhanced. Inbreeding in an infinite population also alters the additive genetic variance through the generation of positive association among genes within a locus. In the present study, the joint effect of selection, linkage and partial inbreeding (partial selfing or partial full-sib mating) on the additive genetic variance was modeled. The recurrence relations of the additive genetic variance between successive generations and the prediction equation of the asymptotic additive genetic variance were derived. Numerical computation showed that although partially inbred populations initially maintain larger genetic variances, the accumulated effect of selection overrides the effect of inbreeding. Stochastic simulation was carried out to check the precision of prediction, showing that the obtained equations give a satisfactory prediction during initial generations. However, the predicted values always overestimate the simulated values, especially in later generations. Based on these results, possible extensions and perspectives of the assumed model were discussed.

Animals↗
PubMed2006

Precipitants and additives for membrane crystallization of lysozyme.

Membrane crystallization is a newly developed crystallization technique that has proven to be superior in producing good crystal forms under operating conditions that are not appropriate to perform the crystallization process by other traditional techniques. In this work, static membrane crystallization was carried out on lysozyme, with hollow-fiber microporous hydrophobic membranes. Numerous precipitant and additive types and concentrations were employed in the crystallization processes in order to select the most appropriate precipitant and additive types and to find their corresponding concentration levels that can yield the best crystal forms. The crystallization processes were analyzed in two ways: firstly, by evaluation of the transmembrane fluxes obtained by using different precipitants and additives; secondly, by utilization of the images and results obtained from the micrography and IR spectra in comparisons and evaluations of the crystals formed under all kinds of conditions. Moreover, the size distributions of the crystals yielded under several typical crystallization conditions were analyzed, and turbidity and induction time periods obtained during typical crystallization experiments were also measured. Amongst the numerous precipitants and additives tested, the most appropriate precipitant type and additive were chosen and their concentrations were optimized. Good lysozyme crystals were obtained using a certain precipitant and additive. The obtained results from this work further support the advantages of utilizing the membrane crystallization technique for macromolecule crystallizations.

Biotechnology↗
PubMed1982

Neuronal addition and retinal expansion during growth of the crucian carp eye.

Using standard paraffin technique the addition of new cells in crucian carp retinas was examined. Between eye diameters 4.4 and 10.0 mm the number of ganglion cells increases from 103,000 to 205,000, INL cells from 1.5 to 3 million, comes from 250,000 to 900,000, and rods from 2 to 9 million. Concomitantly retinal area increases fivefold and the cell densities decrease by 37% for the cones, 57% for the INL cells, and 58% for the ganglion cells, while the rod density remains stable. In relation to the rods the cell ratios at different retinal loci undergo marked changes during growth. The contributions to retinal growth by addition of new neurons and by expansion of the retina have been determined for the different retinal layers. The layer of rods grows exclusively by addition of new rod mosaic. In the cone layer 81% of growth is due to addition of new cone mosaic. In the inner nuclear layer (INL) 56% of growth is due to addition of new cells and in the ganglion cell layer 52% is due to cell addition. In each case retinal expansion accounts for the remainder of increase in retinal area. On morphological grounds six cone types can be found in the crucian carp retina. Their ratios are constant during retinal growth and at different retinal loci.

Animals↗
PubMed1998

The effects of a mixture of charged and neutral additives on analyte migration behavior in capillary electrophoresis.

Multicomponent additives, such as derivatized cyclodextrins with various degrees of substitution, can be considered single-component additives as long as the fraction of each component remains constant. In this paper, equations are derived describing the effect of such additives on the migration behavior of analytes. These equations are used in the study of capillary electrophoresis (CE) systems with differentially charged cyclodextrins as additives. For weakly acidic analytes, the binding with highly negatively charged sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) increases their negative electrophoretic mobility, while the binding with neutral hydroxypropyl-beta-cyclodextrin (HP-beta-CD) decreases their negative mobility. By obtaining the equilibrium constants and mobilities for each additive with each analyte (in this case, phenol, 2-naphthol and 1-naphthol), the migration behavior of these analytes in CE systems is quantitatively predicted at various concentrations of mixtures of the two additives. The properties of the contour lines in the binding isotherm surfaces of such CE systems are discussed.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2002

Supra-additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro.

The effect of concurrent paclitaxel and cisplatin was tested in vitro in 5 vulvar squamous cell carcinoma (SCC) cell lines (UM-SCV-1A, -2, -4 and -7 and UT-SCV-3). Chemosensitivity was tested using the 96-well plate clonogenic assay. Paclitaxel concentrations used varied between 0.4 and 1.6 nM, and cisplatin concentrations varied between 0.1 and 0.9 microg/ml. These drug concentrations are clinically achievable. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the 2 drugs with the survival fraction (SF) of paclitaxel alone. With all cell lines tested the growth-inhibitory effect of simultaneous paclitaxel and cisplatin was at least additive. The effect of the tested combination on the UM-SCV-1A and UT-SCV-3 cell lines was clearly supra-additive with all paclitaxel concentrations tested, and the UM-SCV-4 and UM-SCV-7 cell lines exhibited a supra-additive effect with increasing paclitaxel concentrations. The degree of supra-additivity was dose-dependent in the UM-SCV-7 cell line with increasing synergy at higher paclitaxel doses. In the current study the combination of paclitaxel and cisplatin had a clear additive or supra-additive cytotoxic effect on the vulvar SCC cell lines, and it has been successfully used in other gynecologic malignancies; therefore concurrent paclitaxel and cisplatin also deserves further testing in clinical settings in advanced-stage vulvar carcinoma, which has a poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Stabilization of 5-azacytidine by nucleophilic addition of bisulfite ion.

5-Azacytidine (I) stability was increased approximately 10-fold over its stability in water or lactated Ringer injection by the addition of excess sodium bisulfite and the maintenance of pH approximately 2.5. The increased stability in the presence of bisulfite at pH 2.5 was attributed to the addition of bisulfite across the 5-6 protonated imine bond of I, which prevented the hydrolytic attack on this labile double bond. However, above pH 4, bisulfite increased I degradation. At higher pH, the compound was no longer protonated and bisulfite did not form the stable addition product. The addition compound quickly decomposed above pH 6 to give back the parent compound and, thus, acted as a I prodrug. The intact drug remaining was assayed by high-pressure liquid chromatography (HPLC), and the reversibility of the bisulfite-I addition product above pH 6 was demonstrated by UV spectrophotometry and HPLC. The potential utility of the bisulfite-I addition product as a I prodrug in parenteral and possible oral dosage forms is discussed.

Azacitidine↗
PubMed1987

Swelling studies of gelatin. II: Effect of additives.

Interactions between gelatin and six cationic, anionic, and nonionic drugs or excipients were investigated through their effects on initial swelling rate and equilibrium swelling of gelatin. Short rectangular strips of Type B gelatin containing the additives were immersed in buffer solutions of pH 7.0 at 20 degrees C. Their weight gain due to uptake of buffer solution and their weight loss due to leaching of the additive and of gelatin were determined as a function of time. During preparation of the strips, methyprylon and dicloxacillin sodium crystallized, while octoxynol 9 separated as small droplets in the gelatin matrix. Up to 7% of gelatin leached into the buffer solution during 96 h of immersion from strips of plain gelatin and strips containing five additives. The sixth additive, cetylpyridinium chloride, tripled the amount of gelatin leached while most of this additive remained in the gelatin strip. The other five additives were largely or completely extracted by the buffer solution. Potassium chloride underwent the fastest leaching, being completely dissolved within the first half hour. Octoxynol 9 was extracted most slowly because the swelling solution formed a viscous liquid crystalline phase inside the gelatin. Swelling followed second-order kinetics. Initial swelling rates and equilibrium swelling were calculated with a linearized function. Cetylpyridinium chloride, dodecylammonium chloride, and methyprylon reduced the initial swelling rate of gelatin while dicloxacillin sodium increased it. Octoxynol 9 and potassium chloride left it unchanged. Cetylpyridinium chloride and dodecylammonium chloride reduced the equilibrium swelling of gelatin substantially. Dicloxacillin sodium and octoxynol 9 increased it substantially, while potassium chloride and methyprylon increased it slightly. The extensive interaction of the cetylpyridinium ion with gelatin may result in reduced bioavailability.

Cetylpyridinium↗