Human potency predictions for aldehydes using the local lymph node assay.
The murine local lymph node assay (LLNA) assesses skin sensitization potential as a function of proliferative responses induced in lymph nodes draining the site of topical exposure to test chemical. It has been shown that interpolation of LLNA dose-response data to define the concentration of test chemical required to induce a 3-fold stimulation of proliferation (EC3) offers the prospect of a quantitative index of the relative potency of a contact allergen. Initial studies have demonstrated that there exists a strong (inverse) correlation between EC3 values and contact allergenic potency in humans. Thus, materials with a low EC3 value were more potent contact allergens in humans. However, it is necessary to examine a wide range of allergens to demonstrate that such correlations are generally true. Thus, in the present study, 10 aldehydes of varying degrees of allergenicity in man were evaluated in the LLNA and their EC3 values derived. Formaldehyde was regarded as the strongest allergen in man and also had the lowest EC3 value, 0.35% (equivalent to 0.93% formalin). In contrast, the extremely weak allergen vanillin and the non-sensitizer ethyl vanillin both had EC3 values of >50%. For the remaining 7 aldehydes, there was a close similarity between what is judged to be their rank order of allergenicity in humans and EC3 values derived from analysis of LLNA data. These results support further the utility of EC3 determinations in the LLNA as a measure of the relative potency of a contact allergen.
Basketter
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DA
SEAC Toxicology Unit, Unilever Research, Colworth House, Sharnbrook, Bedfordshire, MK44 1LQ, UK.
Wright
Z M
ZM
Warbrick
E V
EV
Dearman
R J
RJ
Kimber
I
I
Ryan
C A
CA
Gerberick
G F
GF
White
I R
IR
D000447:Aldehydes / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008808:Mice, Inbred CBA; D011237:Predictive Value of Tests
D000447:Aldehydes; D000485:Allergens; D005557:Formaldehyde