Optimised testing strategies for skin sensitization--the LLNA and beyond.
As toxicology in the 21st century progresses towards a future which aims at avoiding the use of in vivo testing, the endpoint of skin sensitisation can now be found in the front line. Accordingly, it was appropriate for several industry sectors to meet and review what has been learned from the currently most widely used in vivo method, the local lymph node assay (LLNA), and to consider the status of progress as we attempt to move beyond that test. No toxicology test is perfect, an experience brought into focus by issues of false positives and, to a lesser extent, false negatives in the LLNA. Use of weight of evidence arguments for classification and labelling, as well as for risk assessment was emphasised and it was also noted that a sufficient body of evidence now exists for conduct of methods other than the LLNA for carefully defined chemical classes. In terms of in vitro alternatives, progress towards methods which will deliver mainly hazard identification is being made, with some entering the final stages of validation, whereby (Q)SAR tools still need improvement to be used on a large scale in practise. As various other challenges also remain, e.g. testing lipophilic substances, as well as the development of non-animal methods which deliver reliable information on potency for risk assessment, these will remain a topic for continuing research and development.
DABMEB Consultancy Ltd., Sharnbrook, UK. dabmebconsultancyltd@me.com
David
D
Basketter
Jonathan
J
Crozier
Bruno
B
Hubesch
Irene
I
Manou
Annette
A
Mehling
Julia
J
Scheel
D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D000826:Animal Testing Alternatives; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000473:pathology; D005188:False Negative Reactions; D005189:False Positive Reactions; D007114:Immunization / Q000379:methods*; D023441:Local Lymph Node Assay; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D012871:Skin Diseases / Q000139:chemically induced* / Q000276:immunology; D018675:Toxicity Tests
D000485:Allergens