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Final report on the safety assessment of benzaldehyde.

Benzaldehyde is an aromatic aldehyde used in cosmetics as a denaturant, a flavoring agent, and as a fragrance. Currently used in only seven cosmetic products, its highest reported concentration of use was 0.5% in perfumes. Benzaldehyde is a generally regarded as safe (GRAS) food additive in the United States and is accepted as a flavoring substance in the European Union. Because Benzaldehyde rapidly metabolizes to Benzoic Acid in the skin, the available dermal irritation and sensitization data demonstrating no adverse reactions to Benzoic Acid were considered supportive of the safety of Benzaldehyde. Benzaldehyde is absorbed through skin and by the lungs, distributes to all well-perfused organs, but does not accumulate in any specific tissue type. After being metabolized to benzoic acid, conjugates are formed with glycine or glucuronic acid, and excreted in the urine. Little acute toxicity was seen. The oral LD(50) of Benzaldehyde in rats and mice ranged from 800 to 2850 mg/kg. The intraperitoneal LD(50) in white rats was 3265 mg/kg. In short-term oral studies, the no observed adverse effect level (NOAEL) was 400 mg/kg in rats and mice. In subchronic oral studies, the NOAEL was 400 mg/kg in rats and 600 mg/kg in mice. In a 16-week feeding study, rats given up to 10,000 ppm showed no signs of toxicity. Repeated inhalation of volatilized Benzaldehyde produced ocular and nasal irritation at 500 ppm and death in rabbits at 750 ppm. Undiluted Benzaldehyde was irritating to rabbit eyes, causing edema, erythema, and pain. Benzaldehyde was determined not to be a contact sensitizer, but did produce allergic reactions in a maximization test. Clinical reports of allergy to Benzaldehyde are rare. Benzoic Acid did not produce irritation or sensitization reactions in human clinical studies. Benzoic Acid also failed to produce reactions in phototoxicity and photosensitization tests. Neither Benzaldehyde, Benzoic Acid, nor Sodium Benzoate are reproductive or developmental toxicants at doses that are nontoxic to the mother. In a behavioral study, blood levels of 0.12 ng/ml Benzaldehyde produced a 44% reduction in motor activity in mice. Benzaldehyde did not produce mutations in bacterial assays, but did produce chromosomal abnormalities in Chinese hamster cells and increased mutations in a mouse lymphoma forward mutation assay. Benzaldehyde was evaluated by the National Toxicology Program, which found no evidence of carcinogenicity in rats, and some evidence of carcinogenicity in mice. Several studies have suggested that Benzaldehyde can have carcinostatic or antitumor properties. Overall, at the concentrations used in cosmetics, Benzaldehyde was not considered a carcinogenic risk to humans. Although there are limited irritation and sensitization data available for Benzaldehyde, the available dermal irritation and sensitization data and ultraviolet (UV) absorption and phototoxicity data demonstrating no adverse reactions to Benzoic Acid support the safety of Benzaldehyde as currently used in cosmetic products.

Animals↗

MIC determination, disc sensitivity testing, and analysis of regression in cefazedone and cefazolin.

Minimum inhibitory concentrations (MIC) of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl-a1-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen)), a new semisynthetic cephalosporin derivative were determined by a broth dilution technique. In comparison with cefazolin 130 gram-positive and gram-negative bacteria, recent clinical isolates, were tested. In parallel, inhibition zones for the same organisms were determined by a standardized disc technique using 30-micrograms discs. According to the calculated regression lines a good correlation was found for cefazedone and cefazolin between the MIC values and the diameters of the inhibition zones (correlation coefficients r = --0.90 and --0.92, respectively). Taking into account the dosages recommended for cefazedone and the mean serum concentrations to which they give rise, appropriate categories of sensitivity (break points) for susceptibility testing are recommended.

Bacteria↗

[Isolation of beta lactamase enzyme in strains of Staphylococcus aureus with the method of starch paper].

The authors worked with 2,273 strains of Staphylococcus aureus isolated from clinical samples processed at the Microbiology laboratory of Centro Habana Pediatric Teaching Hospital in the period ranging from June 1985 to December 1986. All strains underwent the bacterial sensitivity test against antibiotics by Bauer-Kirby technique. Fourty-eight strains were sensitive to penicillin - which accounts for 2.11% - by the beta-lactamase detection test by the starch paper method. In all cases, negative results were obtained, which is in agreement with the results of the sensitivity tests.

Microbial Sensitivity Tests↗

[Growth of some pathogenic microorganisms on chemically defined media which were proposed for sensitivity testing (author's transl)].

The growth of 16 bacterial cultures, which belong to the frequently encountered pathogens, in three different chemically defined fluid media was investigated through turbidity measurements in comparison with Mueller-Hinton-broth. E. coli, Salm. dublin, Salm. typhi-murium, Enterobacter cloacae, Proteus mirabilis, Pseud. aeruginosa and Bac. cereus grew in two of the three tested defined media with approximately the same intensity as in the Mueller-Hinton broth. Staph. aureus grew well only in one of the 3 tested defined media. Listeria monocytogenes, Erysipelothrix rhusiopathiae, Pasteurella multocida, Neisseria gonorrhoeae and Brucella abortus showed only in one of the three tested media a barely descernible growth, whereas Strept. faecalis, Strept. pneumoniae, Strept. pyogenes showed no growth in the three tested defined media after 34 hours of incubation. None of the tested defined media can be used for routine sensitivity testing but the use of two of the three tested defined media as a reference medium for the standardization of the complex sensitivity testing media remains theoretically possible.

Bacteria↗

Effective method for discriminating between oral bacterial and human alkaline phosphatase activity.

Alkaline phosphatase (ALPase) activity was quantitatively compared in various kinds of oral bacteria. High ALPase activity was detected in 3 species of periodontal bacteria, Porphyromonas gingivalis, Prevotella intermedia and Capnocytophaga sputigena. The ALPase activity detected in these bacteria was almost completely inhibited in the presence of 1% sodium dodecyl sulfate (SDS). By contrast, the activity of mammalian ALPase isoenzymes was not inhibited at all even in the presence of 1% SDS. These results indicate that the ALPase assay in combination with 1% SDS can identify the origin of ALPase detected in gingival crevicular fluid as being from bacteria or from a host response. Clinical examination with adult periodontitis revealed that ALPase activity in gingival crevicular fluid from the patients consisted of a combination of SDS-sensitive and SDS-resistant activities. These findings indicate that ALPase activity detected in gingival crevicular fluid originates not only from bacteria but also from a host response.

Adult↗

The LIV-I/LS system as a determinant of azaserine sensitivity of Escherichia coli K-12.

The growth of Escherichia coli is inhibited by an antibiotic compound, azaserine (O-diazoacetyl-L-serine). Previous studies revealed the biochemical properties of azaserine, which involves inhibition of various enzymatic reactions as well as introduction of DNA breakage. However, genetically, nothing has been elucidated except that all the azaserine-resistant strains isolated so far carry lesions in the aroP gene as a primary determinant. Here, we demonstrate that, in addition to AroP, the LIV-I/LS system, an ATP-binding cassette type transporter, is involved in azaserine sensitivity of E. coli, by genetic analysis and transport studies, in which Ki value for azaserine was determined to be approximately 10(-3) M.

Amino Acid Transport Systems↗