Sulfacetamide Research Articles

Dermal tolerability and safety of a fragrance-free sulfacetamide/sulfur cleanser

The objective of this single-center, investigator-blinded study involving 157 randomized, healthy patients was to determine the dermal safety of a new 10% sodium sulfacetamide and 5% sulfur cleanser, compared with (10% sodium sulfacetamide and 5% sulfur) and 0.2% sodium lauryl sulfate (SLS). This study involved 3 phases. In the first phase, induction/irritation, the cleansers in 8% dilution and SLS were applied under separate semi-occlusive patches on the backs of subjects 3 times per week for 3 weeks. Each application remained on the skin for 8 hours, after which the patient washed it off. The test sites were observed 48 hours later (72 hours on weekends) for signs of irritation or inflammation. The second phase involved a rest period of 10 to 14 days, during which no patches were applied. During the third challenge phase, the cleansers were applied to new sites on the back for 48 hours. After patch removal, the sites were observed for signs of sensitization. Very few reactions were observed with any of the test products. There were no observed cases of contact sensitization, and there were only rare incidences of mild irritant reactions. 10% sodium sulfacetamide and 5% sulfur cleanser cleanser was not associated with any signs of irritation. 10% sodium sulfacetamide and 5% sulfur cleanser is the first fragrance-free sulfacetamide/sulfur cleanser for use in patients with rosacea. This study demonstrates that this newest cleanser has a very low potential for irritation or sensitization.

Patient acceptability of a new fragrance-free sulfacetamide/sulfur cleanser

The objective of this study was to evaluate the patient acceptability of a 10% sodium sulfacetamide and 5% sulfur cleanser in patients with mild-to-severe rosacea. This was a single-center, open-label, 4-week study involving 34 enrolled patients (31 of whom completed all visits). All patients were prescribed (metronidazole gel 0.75%) to be used twice daily after washing with the sulfacetamide/sulfur cleanser. The investigator’s assessment of product tolerability involved a 4-point scale to evaluate dryness, scaling, pruritis, and stinging/burning. Patients were asked to assess various skin sensations after product use (eg, “feels soft/smooth‘) on a 6-point scale. In addition, the investigators performed an inflammatory lesion count and assessed erythema severity and global rosacea severity. Investigator assessment of product tolerability showed that the average score for each potential adverse effect decreased over the course of the study. Patient evaluation demonstrated that the average score for each subjective assessment decreased from or remained similar to baseline at the week 4 visit. There was a numerical trend toward improvement in disease-state evaluations (lesion counts, erythema severity score, and global rosacea severity score) over the course of the study.

Comparison of the irritation potential of five topical rosacea products

Rosacea is a common skin disease characterized by increased sensitivity, inflammatory lesions and erythema of the face. The disease is exacerbated by sunlight exposure, hot foods and drinks, and irritating cosmetic products. Topical metronidazole and/or sodium sulfacetamide/sulfur are commonly used to treat the condition. There are several different formulations available of each on the market. Products used to treat rosacea should have minimal to no irritation potential in order to avoid exacerbating the disease. In addition, patients should use sunscreen daily.A new product for the treatment of rosacea has recently been introduced which contains sodium sulfacetamide 10%/sulfur 5% and full-spectrum sunscreens. The irritation potential of this new product was compared to other commonly used products in the treatment of rosacea.A 21 day cumulative irritation patch test study was conducted comparing 5 products used for the treatment of rosacea: the new sodium sulfacetamide 10%/sulfur 5% cream with sunscreens, metronidazole 0.75% cream, metronidazole 0.75% gel, metronidazole 1% cream and sodium sulfacetamide 10%/sulfur 5% suspension without sunscreens. There were 28 subjects enrolled in the study.All products produced little irritation after 21 days of application under a semi-occlusive patch. The products containing metronidazole and the new sodium sulfacetamide/sulfur/sunscreen product had similar minimal to none irritation levels. The sodium sulfacetamide/sulfur suspension without sunscreens produced statistically significantly (p <0.001) more irritation than the new sodium sulfacetamide/sulfur/sunscreen product.The 21 day cumulative irritation patch test study is but one of several methods used to determine the irritation tendency of new topical products. However, for purposes of product comparisons, this test reflects the relative potential for irritation and thus may help the clinician choose the best product for rosacea patients with very sensitive skin. Rosacea is a common skin disease characterized by increased sensitivity, inflammatory lesions and erythema of the face. The disease is exacerbated by sunlight exposure, hot foods and drinks, and irritating cosmetic products. Topical metronidazole and/or sodium sulfacetamide/sulfur are commonly used to treat the condition. There are several different formulations available of each on the market. Products used to treat rosacea should have minimal to no irritation potential in order to avoid exacerbating the disease. In addition, patients should use sunscreen daily. A new product for the treatment of rosacea has recently been introduced which contains sodium sulfacetamide 10%/sulfur 5% and full-spectrum sunscreens. The irritation potential of this new product was compared to other commonly used products in the treatment of rosacea. A 21 day cumulative irritation patch test study was conducted comparing 5 products used for the treatment of rosacea: the new sodium sulfacetamide 10%/sulfur 5% cream with sunscreens, metronidazole 0.75% cream, metronidazole 0.75% gel, metronidazole 1% cream and sodium sulfacetamide 10%/sulfur 5% suspension without sunscreens. There were 28 subjects enrolled in the study. All products produced little irritation after 21 days of application under a semi-occlusive patch. The products containing metronidazole and the new sodium sulfacetamide/sulfur/sunscreen product had similar minimal to none irritation levels. The sodium sulfacetamide/sulfur suspension without sunscreens produced statistically significantly (p <0.001) more irritation than the new sodium sulfacetamide/sulfur/sunscreen product. The 21 day cumulative irritation patch test study is but one of several methods used to determine the irritation tendency of new topical products. However, for purposes of product comparisons, this test reflects the relative potential for irritation and thus may help the clinician choose the best product for rosacea patients with very sensitive skin.

Radiosterilization of sulfonamides: I: determination of the effects of gamma irradiation on solid sulfonamides

Three antibiotics sulfafurazole (SFZ), sulfamethoxazole (SMZ) and sulfacetamide sodium (SSA-Na) belonging to sulfonamides were irradiated and changes in physico-chemical properties, pH, melting points, UV, IR, NMR, TLC, GC-MS, ESR characteristics, antimicrobial activities of active components were studied at normal and accelerated stability test conditions. Two radiolytic intermediates for both SFZ and SMZ and four radiolytic intermediates for SSA-Na were found in the irradiated solid samples after the GC-MS analysis. The results obtained under normal and accelerated stability test conditions were observed to be consistent with the unirradiated values.

3-Aminophenol as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives

A rapid, simple and sensitive spectrophotometric method for the determination of some sulfa drugs is described. The method is based on the formation of orange yellow colored azo product by the diazotization of sulfonamides, viz., dapsone (DAP), sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG) and sulfadimidine (SFDd) followed by a coupling reaction with 3-aminophenol in aqueous medium. Absorbance of the resulting orange yellow product is measured at 460 nm and is stable for 6 days at 27 °C. Beer's law is obeyed in the concentration range of 0.05–8.0 μg/ml at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfonamides in various pharmaceutical preparations and common excipients used as additives in pharmaceuticals do not interfere in the proposed method. Plausible reaction mechanism is proposed for the formation of the azo product.

Topical acne drugs: review of clinical properties, systemic exposure, and safety.

This review examines the commonly available topical acne agents and factors that determine their percutaneous absorption. Reported and theoretical adverse effects from systemic exposure are detailed. The topical retinoid class, which includes tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin and erythromycin, are regulated by prescription in most countries. Used appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of active ingredient into the circulation. Clear-cut links to systemic toxicity in humans are practically nonexistent, except in the case of topical clindamycin, which has been associated with diarrhea rarely, and there have been 2 cases of pseudomembranous colitis reported. Birth defects have occurred in two patients treated with tretinoin and one patient treated with adapalene, but causation was not proven. Another prescription drug, 20% azelaic acid, is associated with relatively high systemic exposure, which is presumed innocuous because it is a normal dietary constituent whose endogenous levels are not altered by topical use. Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are available in concentrations of 2% or more in over-the-counter acne treatments and some prescription products. All of these agents are known to exhibit some degree of percutaneous absorption. They remain largely unregulated because, other than skin irritation, only local allergic contact dermatitis from benzoyl peroxide in about 2.5% of patients and rare local and systemic hypersensitivity reactions from sodium sulfacetamide have been reported. Salicylism has occurred using methyl salicylate ointments and high concentrations of salicylic acid on widespread areas of hyperkeratotic skin, but there are no known cases resulting from salicylic acid acne products. Caution is advised in special circumstances, such as during childhood, pregnancy, lactation and concomitant therapy with other drugs, because relevant studies are lacking. Animal data support avoidance of many topical agents, particularly known teratogens such as retinoids and salicylic acid, in pregnant women. Salicylate avoidance is advised during lactation, because aspirin use carries the risk of bleeding disorders in nursing infants.

A New, Sensitive, and Rapid Spectrophotometric Method for the Determination of Sulfa Drugs

A sensitive, rapid, and simple spectrophotometric method is described for the determination of sulfa drugs. The method is based on the formation of a red-colored product by the diazotization of sulfonamides such as sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG), and sulfamethazine (SFMt), followed by complexation with dopamine in the presence of molybdate ions in (1 + 1) H2SO4 medium. Absorbance of the resulting red product is measured at 490-510 nm, and the product is stable for 2 days at 27 degrees C. Beer's law is obeyed in the concentration range of 0.04-8.0 microg/mL at the wavelength of maximum absorption. The method was used successfully for the determination of some sulfonamides in tablets and eye drops. Common excipients used as additives in pharmaceuticals do not interfere in the proposed method. The method offers the advantages of simplicity, rapidity, and sensitivity without the need for extraction or heating. The limits of detection and quantitation were calculated for SFT, SFD, SFA, SFMx, SFMr, SFG, and SFMt.

A FLOW ANALYSIS SYSTEM FOR THE RAPID DETERMINATION OF SULFONAMIDES USING A SOLID PHASE PHOTOMETRIC SENSING ZONE

ABSTRACT A flow injection analysis system with solid phase spectrophotometric transduction has been developed for the assay of different sulfonamides: sulfanilamide (SN), sulfacetamide (SC), sulfamethoxazole (SM) and sulfadiazine (SD). The sensor consists in a monochannel system using Sephadex QAE A-25 resin as a microsensing zone (inside a flow-through cell) where sulfonamides are temporarily retained. The measurements of the intrinsic absorbance of sulfonamides were made at 263 nm for SC, SD and SM, and 258 nm for SN. Using a NaOH (10−3 mol l−1)/NaCl (0.02 mol l−1) solution as carrier, the determination of sulfonamides was carried out for 40 and 600 µl of sample volume, being the carrier itself the desorbing solution. The detection limits were found to be less than 0.1 and 0.02 µg ml−1 for both sample volumes, respectively, and the linear dynamic range extended between 1–45 µg ml−1 (40 µl) and 0.2–10 µg ml−1 (600 µl). The relative standard deviations (n = 10) lower than 2.3%. A study of the potentially interfering species was carried out, included trimethoprim. The method shows good results on determination of sulfonamides in pharmaceutical preparations and urine.

CHLAMYDIAL NEONATAL CONJUNTIVITIS (CNNC) IN ILORIN, MIDDLE BELT OF NIGERIA

An increasing number of babies with conjunctivitis in our center what require an urgent evaluation was observed. To evaluate Chlamydial aetiology of Neonatal conjunctivitis in our environment all babies born in the University of Ilorin Teaching Hospital over a six months period were prospectively screened for Neonatal conjunctivitis using the Center for Disease Control/World Health Organization case definition for Neonatal conjunctivitis. All patients diagnosed to have Neonatal conjunctivitis had laboratory evaluation done to identify the causes. However only those from whom the inclusion bodies of chlamydia were seen got included in this study. An empirical treatment with 10% sodium sulphacetamide eye drops was given to all patients while other additional illnesses identified were managed in a standard way. Clinical re-evaluation was done by 72 hours and 7 days of treatment for clinical cure. A total number of 112 babies developed neonatal conjunctivitis within the study period among the 852 babies screened and chlamydia was seen in 36 (32%). The hospital based incidence for Chlamydial neonatal conjunctivitis was 42 per thousand live births. There was a male preponderance. Gestational Age ranged between 27 weeks and 44 weeks though there were more term babies. Majority were delivered by spontaneous vertex. The Mean Age of on-set of disease was 5 days with a standard deviation of 3.8 days. Premature rupture of fetal membrane occurred in 1 (3%) case. Fifteen (42%) of 36 mothers had antenatal vaginal discharge. All mothers were married. Purulent eye discharge was the commonest clinical presentation and was sometimes unilateral. All babies responded well to treatment. No complication was observed in any baby. It was concluded that chlamydia trachomatis was the leading cause of neonatal conjunctivitis in our environment and the disease is of a remarkable magnitude requiring attention in our sub region. It has similar outlook with those reported from other regions of the World. (Af. J. of Clinical and Experimental Microbiology: 2002 3(2): 69-71)

Iminodibenzyl as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives

A rapid, selective and simple spectrophotometric method for the determination of sulfa-drugs is described. The method is based on the formation of violet colored azo product by the diazotization of sulfonamides, viz. sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG) and sulfadimidine (SFDd) followed by a coupling reaction with iminodibenzyl in alcohol medium. Absorbance of the resulting violet azo product is measured at 570–580 nm and is stable for 24 h at 27°C. Beer's law is obeyed in the concentration range of 0.05–6.0 μg ml −1 at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfonamides in various pharmaceutical preparations and common excipients used as additives in pharmaceuticals do not interfere in the proposed method. The method offers the advantages of simplicity, rapidity and sensitivity without the need for extraction or heating. A reaction mechanism is proposed for the formation of the violet azo product.

Evaluation of Sodium Sulphacetamide drops in the Treatment of Ophthalmia Neonatorum

Sodium sulphacetamide eye drops had been used successfully in the past in the treatment of ophthalmia neonatorium (ON) but its use has decreased remarkably in recent time. The efficacy of 10 percent sodium sulphacetamide eye drops in the treatment of ON was prospectively evaluated in 68 neonates seen in our Neonatal Intensive Care Unit over a period of six months. Excluded from the study were babies with suspected gonococcal ON, and those who required systemic antibiotics for the treatment of associated sepsis. The eye drops were instilled for one week if by 72 hours of use, clinical response was achieved, otherwise another ophthalmic agent was used. Seventy seven percent of the neonates had clinical cure. It is concluded that sodium sulphacetamide drops may be a useful first line eye drop in the treatment of ON. Nigerian Journal of Paediatrics 2001;28:50. pp. 50-52

New treatments and therapeutic strategies for acne.

Successful management of acne requires careful patient evaluation followed by consideration of several patient and medication factors when selecting a particular therapeutic regimen. Within the last few years, several new agents for the treatment of acne have become available that afford greater flexibility in the treatment of this prevalent dermatologic disorder. These include adapalene, tazarotene, 2 new topical tretinoin formulations, azelaic acid, a new sodium sulfacetamide formulation, and an oral contraceptive recently approved by the Food and Drug Administration for the treatment of acne. After a brief overview of the pathophysiology of acne and existing therapies, this review evaluates the new antiacne agents and how they can be integrated into a successful treatment strategy that takes into account acne severity and predominant lesion type as well as age, skin type, lifestyle, motivation, and the presence of coexisting conditions.

Kinetics ofin vitro drug release from chitosan/gelatin hybrid membranes

In vitro studies of controlled release from chitosan/gelatin hybrid membranes were carried out using drugs of different molecular weight. It was found that release of urea, 5-fluorouracil (5-Fu), sodium benzoate, sodium salicylate, sodium mandelate, and sulfacetamide sodium followed zero-order kinetics after a short time lag. Variation of the diffusion coefficient, permeation coefficient, and degree of hydration with crosslinking and varying weight percent of gelatin in membrane matrices were studied in detail by using 5-Fu as a model drug. The diffusion coefficient and permeation coefficient of 5-Fu are dependent on the degree of hydration of the swollen membrane. The transport process of drug molecules in the hydrogel membrane is presumed to be predominantly of the pore mechanism. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1751–1758, 1998

The treatment of rosacea: the safety and efficacy of sodium sulfacetamide 10% and sulfur 5% lotion (Novacet) is demonstrated in a double-blind study

Rosacea is a chronic skin disease of adults characterized by facial flushing, erythema, telangiectasia, and inflammatory papules and pustules. The open-label use of the combination of topical sodium sufacetamide (10%) and sulfur (5%) has been reported to be helpful in controlling the disorder but observations from well-controlled trials are lacking. This vehicle-controlled double-blind study was performed to determine the safety and efficacy of a novel formulation of this combination in treating rosacea. A total of 103 patients with moderate to severe facial erythema and at least five papules and/or pustules bilaterally were enrolled, and 94 completed the study. Treatment was randomly assigned. Active or vehicle lotion was applied twice daily for the duration of the 8-week trial. Efficacy was evaluated by counting inflammatory lesions, assessing the severity of facial erythema, and by both a physician's and a subject's global evaluation. A product satisfaction questionnaire was also completed by all patients. By week 4 there was significant improvement in all efficacy parameters favoring treatment with active lotion over vehicle lotion and maximum benefit was seen at week 8. Inflammatory lesions had decreased by 65 ± 5.3% (mean ± SEM) in the active treatment group compared with 44 ± 5.0% in the vehicle treatment group by week 4 (P=0.002), and by 78 ± 4.5% vs 36 ± 8.9%, respectively, by week 8 (P<0.001). Facial erythema had decreased by week 4 in 66% of the patients in the active treatment group compared with 33% in the vehicle group (P=0.005) and by week 8 83% vs 31% of each group, respectively, had improved (P<0.001). The most common adverse experiences were application site reactions which decreased in frequency over time. This formulation of topical sodium sulfacetamide (10%) and sulfur (5%) lotion was effective in reducing the inflammatory lesions and erythema of rosacea and was well tolerated and accepted by the patients.

Acetylacetone-formaldehyde reagent for the spectrophotometric determination of some sulfa drugs in pure and dosage forms

A new simple and sensitive spectrophotometric procedure for the determination of sulfacetamide sodium (I), sulfadiazine (II), sulfadimidine (III) and sulfathiazole (IV) is based on the reaction of the drug with acetylacetone-formaldehyde reagent to give a yellow product having λmax at 400 nm. Optimization of the reaction conditions has been investigated. A linear correlation was obtained between absorbance at λmax and the concentration. The Beer's law limits of I, II, III and IV are 4–80, 4–72, 4–60 and 4–80 μg/ml, respectively. For more accurate results, Ringbom optimum concentration ranges were evaluated to be 6–76, 8–66, 6–56 and 8–75 μg/ml for I, II, III and IV, respectively. The molar absorptivities and Sandell sensitivities for all sulfa drugs under consideration were evaluated. Relative standard deviations of 0.98, 1.07, 0.86 and 0.79% were obtained for I, II, III and IV, respectively. The method has been compared to the official method and found to be simple, accurate (t-test) and reproducible (F-test). The developed procedures were applied for bulk sulfa drugs and some of their dosage forms without interferences from additive and common prescribed drugs.

High-performance micellar liquid chromatography determination of sulphonamides in pharmaceuticals after azodye precolumn derivatization

A chromatographic procedure with precolumn derivatization to form the N-(1-naphthyl)ethylenediamine dihydrochloride azodyes is proposed for the analysis of several sulphonamides (sodium sulphacetamide, sulphadiazine, sulphaguanidine, sulphamerazine, sulphamethizole, sulphamethoxazole, sulphanilamide and sulphathiazole) in pharmaceutical preparations (tablets, pills, capsules, suspensions and drops). The separation is performed with a 0.05 M sodium dodecyl sulphate/2.4% pentanol eluent at pH 7. The precolumn derivatization improved the resolution in the chromatograms and increased the selectivity in the determination of mixtures of sulphonamides and in preparations where other drugs were present. The derivatization reaction was readily performed in a micellar medium of SDS at pH 1, leading to a rapid and simple procedure. The recoveries were in the 97–104% range with relative standard deviations usually below 3%.

Confirmatory Method for Sulfonamide Residues in Animal Tissues by Gas Chromatography and Pulsed Positive Ion-Negative Ion-Chemical Ionization Mass Spectrometry

A confirmatory method has been developed for determination of 13 sulfonamides in edible tissues. The assay involves extraction from a solution resulting from a screening procedure by liquid chromatography and subsequent derivatization. Sulfachloropyridazine (SCP), sulfadiazine (SDA), sulfadimethoxine (SDM), sulfamethazine (SMZ), sulfamerazine (SME), sulfamethoxazole (SMX), sulfamethoxypyridazine (SMP), sulfapyridine (SPR), sulfaquinoxaline (SQX), and sulfathiazole (STA) were detected as the N1-methyl-N4-trifluoroacetyl derivatives, sulfaguanidine (SGU) as the same derivative after cyclization by hexafluoroacetylacetone, and sulfacetamide (SAC) as the methyl derivative. These sulfonamides were detected by gas chromatography and pulsed positive ion-negative ion-chemical ionization mass spectrometry with methane as the reactant gas, whereas sulfanilamide (SAA) was determined as the methyl derivative by electron-impact ionization.

Spectrofluorimetric determination of sulphonamides in pharmaceutical compounds and foods

Spectrofluorimetry and room temperature photochemically-induced fluorescence (RTPF) have been applied to the determination of sulphacetamide (SAC), sulphaguanidine (SG) and sulphamethazine (SMT) in milk and pharmaceutical formulations. The methods are suitable for determining 0.02–0.10 μg ml of SAC, 0.10–0.50 μg ml of SG, and 0.40–1.00 μg ml of SMT.

The effective antibacterial spectrum of sulfacetamide

Swabs of the anterior eye segment of 180 eyes (145 patients) taken in the time period between August 1, 1989 until August 30, 1989 were sent to an external, independent microbiological institute in order to verify in-vitro antibacterial properties of marketed sulfacetamide containing drugs. MIC test was performed with isolated pathogenic bacterial strains without knowledge of the underlying diagnosis. It was shown that sulfacetamide is able to inhibit the growth of all isolated strains. Depending on the type of bacteria concentrations of 0.006 up to 6.4% sodium sulfacetamide proved to be effective. Simultaneously, all patients were treated with sulfacetamide containing ointment and/or eye drops 4 times daily for maximum of 14 days. With swabs taken at intervals of 7 and 14 days no bacterial growth was detected.

Disinfectants and therapeutic agents for controlling Labyrinthuloides haliotidis (Protozoa: Labyrinthomorpha), an abalone pathogen

Labyrinthuloides haliotidis, a pathogenic parasite of juvenile abalone ( Haliotis kamtschatkana and Haliotis rufescens), was destroyed by a 20-min exposure to 25 mg chlorine per l of sea water. This parasite showed high resistance to six other potential disinfectants: formalin, iodophor, isopropanol, methylene blue, malachite green, and copper sulfate. The antibiotic fungicide cycloheximide at 1–2 mg per l for 23 h per day on 5 consecutive days proved efficacious. However, this treatment had three disadvantages: (1) it was detrimental to some diatoms upon which the abalone fed, (2) it was ineffective against non-growing but infective zoospores of L. haliotidis and thus reinfection usually occurred within 2–3 weeks following treatment, and (3) it resulted in cycloheximide resistant forms of L. haliotidis. Two different combinations of three sulfonamides (sodium sulfamethazine and sodium sulfathiazole with either sodium sulfapyridine or sodium sulfacetamide), especially in conjunction with neomycin sulfate, partially retarded the progression of the disease. Nine other therapeutic agents (betanaphthol, acriflavin hydrochloride, rivanol, furanace, oxytetracycline, chloramine-B, oxolinic acid, metronidazole, and neomycin sulfate) showed little or no activity against L. haliotidis at concentrations higher than would be feasible for use in an abalone culture facility.