Application of a weight of evidence approach to assessing discordant sensitisation datasets: implications for REACH.
The local lymph node assay (LLNA) is the assay of choice in European regulatory toxicology. As with other toxicology/sensitisation assays, it has a potential for false results, the anionic surfactant sodium lauryl sulphate (SLS) representing a classic example. In the work reported here, examples of false positives in the LLNA are compared to published "benchmarks" such as SLS. Clear false positives (e.g. oleic acid) are also contrasted with examples where data interpretation is more challenging. As the LLNA will be applicable to >30,000 chemicals under REACH, and in the light of animal welfare considerations to do no more than the absolute minimum of animal testing, results from a single LLNA often represent the only available data on sensitisation. This reinforces the need to ensure data from this assay are interpreted intelligently, using scientific analysis of results and considering the weight of evidence, before decisions are made on which substances should be classified as representing a skin sensitisation hazard. In chemical classes where the LLNA has been shown to be an inappropriate assay other standardised methods (e.g. the Buehler or Magnusson and Kligman guinea pig tests [OECD 406]) should be employed as the first choice assays.
Basketter
David
D
DABMEB Consultancy Ltd, Sharnbrook, Bedford MK44 1PR, UK. david.basketter@ukonline.co.uk
Ball
Nicholas
N
Cagen
Stuart
S
Carrillo
Juan-Carlos
JC
Certa
Hans
H
Eigler
Dorothea
D
Garcia
Christine
C
Esch
Harald
H
Graham
Cynthia
C
Haux
Carl
C
Kreiling
Reinhard
R
Mehling
Annette
A
D000485:Allergens / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004781:Environmental Exposure; D005188:False Negative Reactions; D005189:False Positive Reactions; D015386:Hazardous Substances / Q000633:toxicity*; D006801:Humans; D023441:Local Lymph Node Assay; D018570:Risk Assessment / Q000379:methods*; D012867:Skin / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
D000485:Allergens; D015386:Hazardous Substances