Evaluation of a non-invasive human and an in vitro cytotoxicity method as alternatives to the skin irritation test on rabbits.
5 substances were investigated for their primary irritant effect by means of different protocols. The cutaneous blood flow values (CBFV) were measured in humans: in a 1st series of experiments 12 h after application of the pure substances for 48 h and in a 2nd series of experiments 1, 24, 48 and 72 h after application of the 10% diluted substances (subclinical concentration) for 3 h. Rabbit skin erythema scores were obtained 1, 24, 48 and 72 h after application of the undiluted substances for 4 h. The uridine uptake inhibition assay on KB cells was included as a cytotoxicity test. Results obtained for both protocols on humans are compared with each other and with the test data obtained on rabbits, and with the cytotoxicity data. Application of the undiluted substances for 48 h on human skin or for only 3 h at a 10% dilution resulted in the same ranking between the substances. The CBFV in the human correlated very well (r = 0.99) with erythema scores obtained on rabbits. A poor correlation was observed between the in vitro and the in vivo results. From this study, it can be concluded that CBFV measurement is a valid method for the detection of erythema at subclinical concentrations.
Jacobs
G A
GA
Institut voor Hygiëne en Epidemiologie, Afdeling Toxicologie, Brussel, Belgium.
Castellazzi
A
A
Dierickx
P J
PJ
D000826:Animal Testing Alternatives; D000818:Animals; D004890:Erythema / Q000139:chemically induced; D005069:Evaluation Studies as Topic; D006801:Humans; D007509:Irritants; D007624:KB Cells / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D014116:Toxicology / Q000379:methods; D014529:Uridine / Q000378:metabolism
D007509:Irritants; D014529:Uridine