In vitro methods: their relevance and complementarity in ocular safety assessment.
Ocular irritation includes a wide variety of mechanisms some of which can be explored by in vitro methods. For example, the effects on epithelial cells that constitute the outer layers of both the conjunctiva and the cornea may result in direct cytotoxicity or impairment of cellular functions -such as impermeability-, phenomena that can be explored in vitro. Irritancy may also involve inflammation of the conjunctival connective tissue and of the corneal stroma with its vascular and cellular features; effects on the stroma can lead to the opacification of the cornea; this last phenomenon may be the consequence of mechanisms such as modification of the structure of proteins or changes in stroma hydration which in particular is closely related to corneal endothelium metabolic activity. Recovery after eye injury depends partly on the extent of ocular damage and on the residual mitotic activity of the remaining cells. We have studied 41 surfactants, lotions and shampoos in 6 to 8 in vitro methods each one exploring one or two endpoints that could be linked to the ocular irritancy phenomena described above. In vivo ocular irritancy data for these materials from previous studies were compared to in vitro results. The results obtained show that -among the techniques that were investigated and for the categories of substances that were studied- the Het-CAM test and more particularly the endpoint that is related to vascular effects gives the best assessment of acute ocular irritancy (Spearman's rho coefficients between in vivo and in vitro data greater than 0.90); however, cell culture methods, especially one based on short contact time between cells and products and on evaluation of early toxic effects, also proved interesting (Spearman's rho coefficients between in vivo and in vitro data greater than 0.85). Moreover, the isolated cornea opacity and permeability test gave complementary information more related to recovery from surfactant-induced damage. These encouraging results lead us to consider in vitro ocular safety assessment with optimism for the categories of products investigated.
Rougier
A
A
L'OREAL, Basic Research Center, Aulnay Sous Bois, France.
Cottin
M
M
de Silva
O
O
Roguet
R
R
Catroux
P
P
Toufic
A
A
Dossou
K G
KG
D000482:Allantois / Q000187:drug effects*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D003315:Cornea / Q000187:drug effects*; D003318:Corneal Opacity / Q000139:chemically induced*; D006224:Cricetinae; D004848:Epithelium / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity; D007928:Lethal Dose 50; D051379:Mice; D011817:Rabbits; D013501:Surface-Active Agents / Q000633:toxicity*
D007509:Irritants; D013501:Surface-Active Agents