Parabens sensitization

To evaluate linearity, limits of detection (LOD), limits of quantitation (LOQ), and sensitivity, an experiment assessed the responses for different concentrations of two analytes of interest. The analytes employed were methyl paraben and rhodamine 110 chloride. Consecutive 5.0 /jL injections of a series of serial dilutions (four replicates) of this standard mixture containing the analytes described were carried out via a cartridge packed with C18 stationary phase and per-column dimensions of 0.5 mm circular cross section and 80 mm length. 

The calibration sensitivity of the analytical method employed is simply determined as the slope of the calibration curve. For example, in the case of methyl paraben, the value of calibration sensitivity obtained was 1.6 mAl I/min///M (Figure 6.22). Analytical sensitivity is defined as the ratio between calibration sensitivity and the value of the standard deviation obtained at each concentration.10 The value of the standard deviation encountered for a concentration of 0.6 //M was 0.1, resulting in an analytical sensitivity for methyl paraben at 0.6 //M of 16 m. II/min///M. As indicated for LOD and LOQ, the values obtained for linearity and sensitivity depend on the analytes employed and the corresponding method and instrumental parameters. For example, Liu et al.9 evaluated the LOD and LOQ for Drug A (released from OROS) for a particular analytical method employing //Pl.C to be 0.5 //g/ml. and 2.0 //g/mL, respectively. 

Contraindications Sensitivity to parabens (used as preservative in gelatin capsule)... 

Certain substances have been reported to affect eczematous skin, but not normal skin. One example is parabens, a popular preservative that may sensitize eczematous skin, but rarely causes... 

Uptake of the parabens probably proceeds by a general dissolution of an ester into the cell with no specific binding sites at the cell surface. In the deep rough mutants, the increased sensitivity to the parabens probably results from the appearance of phospholipid patches at the cell surface which aid in penetration of the parabens and especially of the most hydrophobic one (the Bu ester). A similar mechanism is likely to account for the uptake of phenolics across the outer membrane into the cells. 

During germination and/or outgrowth, spores become sensitive to biocidal agents [140-143], Some inhibitors (e.g. phenolics and parabens) prevent... 

UV and fluorescent spectroscopy can be employed down to 190 nm because there is no solvent interference. Mass spectrometry is easy because the water provides good ionization. Flame ionization detection (FID) is of particular interest because potentially it offers a sensitive and universal detector. A number of different interfaces have been used, including heated capillaries, which have been examined by Miller and Hawthorne [62], Ingelse et al. [63], and others [64, 65], who separated a range of analytes including alcohols, amino acids, and phenols. An alternative method employing a cold nebuliza-tion of the eluent has been introduced by Bone et al. [66]. They were able to detect both aliphatic and aromatic alcohols, polymers, carbohydrates, parabens, and steroids. 

Benzyl alcohol is the most common antimicrobial preservative present in parenteral formulations (Table 5). This observation is consistent with other surveys. ° Parabens are the second most common preservatives. Surprisingly, thimerosal is also common, especially in vaccines, even though some individuals are sensitive to mercuries. Several preservatives can volatilize easily (such as benzyl alcohol, and phenol) and, therefore, should not be used for lyophilized dosage form. Chlorocresol is purported to be a good preservative... 

Reference is an excellent resource on the safety and adverse reaction to several excipients. Sensitization reactions have been reported for the parabens, thi-merosal, and propyl gallate. Sorbitol is metabolized... 

In the multicenter study of the Information Network of Departments of Dermatology, sensitization rates of preservatives in the standard series were all over 1% in the test population of 11485 patients. Thiomersal was rating highest (5.3%), chloromethyl-isothiazolinone/methyi-sothiazolinone, formaldehyde, and methyl-dibromo-glutaronitrile/phenoxyethanol were next at about 2%, and parabens rating lowest at 1.6%. Glutaral, a biocide... 

Parabens can cause allergic contact dermatitis that can run an insidious course, especially when the parabens are in glucocorticoid ointments. In such cases, treatment leads to a protracted dermatitis without acute exacerbation, so that neither the patient nor the physician suspects parabens as a possible cause. A sensitization index of 0.8% was found in 273 patients with chronic dermatitis (1). 

Hypersensitivity reactions to parahens, generally of the delayed type and appearing as contact dermatitis, have been reported. However, given the widespread use of parabens as preservatives, such reactions are relatively uncommon the classification of parabens in some sources as high-rate sensitizers may be overstated. ... 

Various types of additives introduced in the galenic presentation of drugs such as dyes (e.g., tartrazine) preservatives (e.g., parabens) or filling material (e.g., car-boxymethylcellulose, starch) may function themselves as sensitizers or as inert ma-cromolecular carriers facilitating the formation in vitro of eliciting hapten conjugates. Indeed, it has been shown that carboxymethylcellulose, for example, is an efficient carrier for penicilloyl groups, (Schneider et al. 1971) and may by itself act as sensitizer in cattle (de Weck et al. 1969). 

Topical allergy to preservatives and antiseptics incorporated in vehicles is described in detail in Sects. M, N. In the Finish study of eczema patients over a 3-year period, perfume allergy was detected in 3.6% of the cases, sensitivity to thiomersal in 2%, to wool alcohols in 1.2%, to emulsifiers in 1%, to sorbic acid in 0.8%, and to parabens in 0.3% (Hannuksela et al. 1976a). 

A different picture arose when the Mayo Clinic examined over 700 eczema patients over a 2-year period for sensitivity to vehicle ingredients (Iden and Schroeter 1977). Here, sensitivity to ethylenediamine reached 7.9%, paraben mixtures in 3.3%, dichlorophene in 2.4%, propylene glycol in 1.5%, lanolin in 1.1%, polysorbate (Tween 20) in 1 %, and sorbic acid in 1 %. In the Danish survey (Hjorth and Trolle Lassen 1963) comprising routine patch testing in 1,664 ecze-... 

Schorr WF (1968) Paraben allergy a cause of intractable dermatitis. JAMA 204 859-862 Schorr WF (1970) Dichlorophene (G-4) allergy. Arch Dermatol 102 515-520 Schorr WF (1971) Cosmetic allergy. Arch Dermatol 104 459-466 Schorr WL, Ridgway HB (1977) Tobramydn-neomycin cross sensitivity. Contact Dermatitis 3 133-137... 

Preservatives combine both antimicrobials and antioxidants and are often added to water-containing products such as skin care ointments. In general, contact allergy to preservatives is considered rare. Sensitization to preservatives is often due to the use of products on damaged skin, e.g., eczema or leg ulcers. Patients often present with symptoms of dermatitis of the hands or face. The most frequently used preservatives in cosmetics and topical drugs are parabens, imidazolinidyl urea, quaternium-15, dimethylol-di-methyl (DMDM) hydantoin, phenoxyethanol, met-hylchloroisothiazolinone/methylisothiazolinone, dia-zolinidyl urea, 2-bromo-2-nitropropane-i,3-diol and sorbic acid (Schnuch et al. 1998). Preservatives and antimicrobials are also used in industrial products (called biocides), such as metalwork fluids. 

Chloroacetamide (CAS no. 79-07-2). This is a well-known cosmetic biocide, but sensitization is less common than with parabens. An allergic reaction was reported to deodorant (Taran and Delaney 1997) The patch-test concentration is 0.2% pet. Allergic reactions do occur. 

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