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Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation.
Toxicology 2004; 197(3):229-37T

Abstract

Extensive efforts have been made, recently, to find surfactants with lower irritation potential than those presently commercially available, for use in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of a novel family of dicationic arginine-diglyceride surfactant compounds, 1,2-diacyl,3-O-(l-arginyl)-rac-glycerol with alkyl chain lengths in the range from 8 to 14 carbon atoms, were compared to three commercial surfactants. The end-points used to assess toxicity were the red blood cell lysis assay and uptake of the vital dye neutral red 24h after dosing (NRU), respectively. Two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, were used as in vitro models to predict the potential phototoxicity which could result in irritation, determined by resazurin reduction to resorufin and neutral red uptake (NRU). All tested surfactants had cytotoxicity effects as demonstrated by and decrease of NR uptake, which showed a clear concentration-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC(50)) range from 1 microM(-1) (hexadecyl trimethyl ammonium bromide) to 565 microM(-1) (12,12-l-arginine). Erythrocyte haemolysis also showed a clear concentration-response relationship, the 50% of haemolysis ranged from 37 microM(-1) (10,10-l-arginine) to 151 microM(-1) (sodium lauryl sulphate). Phototoxicity was performed with 12,12-l-acetyl-arginine, the most stable chemical structure. The validated 3T3 NRU photoxicity assay was used and revealed a phototoxic potential.

Authors+Show Affiliations

Department Fisiologia-Divisió IV, Facultat de Farmàcia, Av. Joan XXIII s/N, 08028 Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15033545

Citation

Benavides, T, et al. "Assessment of Primary Eye and Skin Irritants By in Vitro Cytotoxicity and Phototoxicity Models: an in Vitro Approach of New Arginine-based Surfactant-induced Irritation." Toxicology, vol. 197, no. 3, 2004, pp. 229-37.
Benavides T, Mitjans M, Martínez V, et al. Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation. Toxicology. 2004;197(3):229-37.
Benavides, T., Mitjans, M., Martínez, V., Clapés, P., Infante, M. R., Clothier, R. H., & Vinardell, M. P. (2004). Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation. Toxicology, 197(3), pp. 229-37.
Benavides T, et al. Assessment of Primary Eye and Skin Irritants By in Vitro Cytotoxicity and Phototoxicity Models: an in Vitro Approach of New Arginine-based Surfactant-induced Irritation. Toxicology. 2004 May 3;197(3):229-37. PubMed PMID: 15033545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation. AU - Benavides,T, AU - Mitjans,M, AU - Martínez,V, AU - Clapés,P, AU - Infante,M R, AU - Clothier,R H, AU - Vinardell,M P, PY - 2003/10/31/received PY - 2003/11/03/revised PY - 2004/01/21/accepted PY - 2004/3/23/pubmed PY - 2004/4/30/medline PY - 2004/3/23/entrez SP - 229 EP - 37 JF - Toxicology JO - Toxicology VL - 197 IS - 3 N2 - Extensive efforts have been made, recently, to find surfactants with lower irritation potential than those presently commercially available, for use in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of a novel family of dicationic arginine-diglyceride surfactant compounds, 1,2-diacyl,3-O-(l-arginyl)-rac-glycerol with alkyl chain lengths in the range from 8 to 14 carbon atoms, were compared to three commercial surfactants. The end-points used to assess toxicity were the red blood cell lysis assay and uptake of the vital dye neutral red 24h after dosing (NRU), respectively. Two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, were used as in vitro models to predict the potential phototoxicity which could result in irritation, determined by resazurin reduction to resorufin and neutral red uptake (NRU). All tested surfactants had cytotoxicity effects as demonstrated by and decrease of NR uptake, which showed a clear concentration-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC(50)) range from 1 microM(-1) (hexadecyl trimethyl ammonium bromide) to 565 microM(-1) (12,12-l-arginine). Erythrocyte haemolysis also showed a clear concentration-response relationship, the 50% of haemolysis ranged from 37 microM(-1) (10,10-l-arginine) to 151 microM(-1) (sodium lauryl sulphate). Phototoxicity was performed with 12,12-l-acetyl-arginine, the most stable chemical structure. The validated 3T3 NRU photoxicity assay was used and revealed a phototoxic potential. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/15033545/Assessment_of_primary_eye_and_skin_irritants_by_in_vitro_cytotoxicity_and_phototoxicity_models:_an_in_vitro_approach_of_new_arginine_based_surfactant_induced_irritation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300483X04000605 DB - PRIME DP - Unbound Medicine ER -