Discrimination of the irritancy potential of surfactants in vitro by two cytotoxicity assays using normal human keratinocytes, HaCaT cells and 3T3 mouse fibroblasts: Correlation with in vivo data from a soap chamber assay

Körting, Hans Christian; Herzinger, Thomas; Hartinger, A.; Kerscher, Martina; Angerpointner, Thomas A.; Maibach, Howard I.

doi:10.1016/0923-1811(94)90085-x

Cited by 61 publications

(48 citation statements)

References 21 publications

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“…Previous studies have suggested that cultured normal human keratinocytes may be predictive of irritancy caused by various surfactants in human subjects (13) and these monolayer cultures have been compared with in vivo skin irritation data (14,15). A good correlation with in vivo human skin data has been demonstrated for surfactants of different chemical types and irritation potential (16).…”

Section: Introductionmentioning

confidence: 92%

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

et al. 2004

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Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants.Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MTT assay and uptake of the vital dye neutral red 24 h after dosing (NRU).Results. Lysine-derivative surfactants showed higher IC 50 s than did commercial anionic irritant compounds such as sodium dodecyl sulphate, proving to be no more harmful than amphoteric betaines. The aggressiveness of the surfactants depended upon the size of their constituent counterions: surfactants associated with lighter counterions showed a proportionally higher aggressivity than those with heavier ones.Conclusions Synthetic lysine-derivative anionic surfactants are less irritant than commercial surfactants such as sodium dodecyl sulphate and Hexadecyltrimethylammonium bromide and are similar to Betaines. These surfactants may offer promising applications in pharmaceutical and cosmetic preparations, representing a potential alternative to commercial anionic surfactants as a result of their low irritancy potential.

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Section: Introductionmentioning

confidence: 92%

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

et al. 2004

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“…On the other hand, CAPB caused less clinical skin irritation than SLS and BAC: 0,2% BAC >0.5% SLS >0,5% CAPB (35). However, Korting et al (34) reported that CAPB possessed a higher irritation potential than polyethylene glycol (non-ionic surfactant) as measured by an evaporimeter and chromameter. Interestingly, CAPB in vitro proved to be highly cytotoxic compared with other surfactants (34).…”

Section: Amphoteric Surfactants Cocoamidopropyl Betaine (Cap B)mentioning

confidence: 98%

“…However, Korting et al (34) reported that CAPB possessed a higher irritation potential than polyethylene glycol (non-ionic surfactant) as measured by an evaporimeter and chromameter. Interestingly, CAPB in vitro proved to be highly cytotoxic compared with other surfactants (34). The authors ranked the cytotoxicity of different classes of surfactant evaluated by both in vitro neutral red release and cell growth/protein assays as follows: cationic= amphoteric >anionic >non-ionic (according to decreasing cytotoxicity).…”

Section: Amphoteric Surfactants Cocoamidopropyl Betaine (Cap B)mentioning

confidence: 99%

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Surfactants and experimental irritant contact dermatitis

1995

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Surface-active agents (surfactants) are characterized by the possession of 2 different moieties, both polar and non-polar regions on the same molecule. Surfactants are broadly classified as anionic, cationic, amphoteric, or non-ionic, according to the nature of the hydrophile yielded in aqueous solution. In currently marketed household, personal, and industrial cleaners, anionic surfactants are the most common class because of their relative ability to solubilize fats and oils, lower the surface tension of aqueous solutions, or form microemulsions. Many surfactants elicit irritant reactions when applied to the skin, partially due to their relative ability to solubilize lipid membranes. Hence, surfactants have become important implements in skin irritation investigations. In general, the physicochemical properties of surfactants are a crucial factor in eliciting skin irritation. Anionic surfactants are broadly accepted as potent irritants to human and animal skin. Cationic surfactants are reputedly at least equally irritating, but more cytotoxic than anionic, while the irritation potential of non-ionic surfactants is considered the lowest. Such classification of innumerable surfactants is convenient and held in high practical esteem. However, the categorization does not permit the exact determination of irritation and cytotoxicity potential of each surfactant. Ranking of surfactant skin irritancy and cytotoxicity obtained by both in vitro and in vivo assays provides a helpful orientation for future work.Key words: anionic, cationic, amphoteric, non-ionic surfactants; skin irritation; in vivo skin irritation test; in vitro cytotoxicity assays; ranking of surfactant skin irritancy. © Munksgaard, 1995.

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“…Cell cultures have been widely used to evaluate irritation potential of formulations and their components (26,27). A good correlation between in vitro cytotoxicity assays and in vivo skin irritation has been demonstrated for surfactants of different irritation potential, and since then, cytotoxicity assays became largely used to predict the irritation potential of substances (28).…”

Section: Discussionmentioning

confidence: 99%

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

et al. 2009

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Abstract. We evaluated the ability of microemulsions containing medium-chain glycerides as penetration enhancers to increase the transdermal delivery of lipophilic (progesterone) and hydrophilic (adenosine) model drugs as well as the effects of an increase in surfactant blend concentration on drug transdermal delivery. Microemulsions composed of polysorbate 80, medium-chain glycerides, and propylene glycol (1:1:1, w/w/w) as surfactant blend, myvacet oil as the oily phase, and water were developed. Two microemulsions containing different concentrations of surfactant blend but similar water/oil ratios were chosen; ME-lo contained a smaller concentration of surfactant than ME-hi (47:20:33 and 63:14:23 surfactant/oil/water, w/w/w). Although in vitro progesterone and adenosine release from ME-lo and MEhi was similar, their transdermal delivery was differently affected. ME-lo significantly increased the flux of progesterone and adenosine delivered across porcine ear skin (4-fold or higher, p<0.05) compared to progesterone solution in oil (0.05±0.01 μg/cm 2 /h) or adenosine in water (no drug was detected in the receptor phase). The transdermal flux of adenosine, but not of progesterone, was further increased (2-fold) by ME-hi, suggesting that increases in surfactant concentration represent an interesting strategy to enhance transdermal delivery of hydrophilic, but not of lipophilic, compounds. The relative safety of the microemulsions was assessed in cultured fibroblasts. The cytotoxicity of ME-lo and ME-hi was significantly smaller than sodium lauryl sulfate (considered moderate-to-severe irritant) at same concentrations (up to 50 μg/mL), but similar to propylene glycol (regarded as safe), suggesting the safety of these formulations.

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Discrimination of the irritancy potential of surfactants in vitro by two cytotoxicity assays using normal human keratinocytes, HaCaT cells and 3T3 mouse fibroblasts: Correlation with in vivo data from a soap chamber assay

Cited by 61 publications

References 21 publications

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

Assessment of the Potential Skin Irritation of Lysine-Derivative Anionic Surfactants Using Mouse Fibroblasts and Human Keratinocytes as An Alternative to Animal Testing

Surfactants and experimental irritant contact dermatitis

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

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