The identification of photoallergic potential in the local lymph node assay.
Guinea pig test methods are the most commonly used and reliable of predictive models for contact photoallergenicity of chemicals. The murine local lymph node assay (LLNA) has been developed recently as an alternative method for the identification of skin-sensitizing chemicals. Sensitization potential is measured from an assessment of the proliferation of lymphocytes in lymph nodes draining the site of exposure to the test chemical. This work investigates the activity of 6 widely reported photoactive chemicals in a modified LLNA (a photo-LLNA). The photoallergens tetrachlorosalicylanilide and fentichlor elicited positive ultraviolet radiation (UV)-dependent proliferative responses that were greater than their positive UV-independent responses, suggesting that they are both contact and photoallergic in the mouse. The lack of a proliferative response to 6-methylcoumarin and the absence of a reproducible response to musk ambrette suggest that the assay is insufficiently sensitive to identify weak photoallergic potential. Positive UV-dependent responses to acridine and anthracene, both photoirritants, cast doubt on the specificity of the photo-LLNA. Positive LLNA responses to these chemicals may be due to skin protein modification, based on evidence from the in vitro photo-chemical protein-binding assay. These results demonstrate that the photo-LLNA is able to detect at least moderate photoallergic potential.
Scholes
E W
EW
Environmental Safety Laboratory, Unilever Research and Engineering, Sharnbrook, Bedford, United Kingdom.
Basketter
D A
DA
Lovell
W W
WW
Sarll
A E
AE
Pendlington
R U
RU
D000166:Acridines / Q000633:toxicity; D000485:Allergens / Q000187:drug effects; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D002455:Cell Division; D002733:Chlorophenols / Q000633:toxicity; D003374:Coumarins / Q000633:toxicity; D004136:Dinitrobenzenes / Q000633:toxicity; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D010787:Photosensitivity Disorders / Q000175:diagnosis* / Q000473:pathology; D011485:Protein Binding; D012458:Salicylanilides / Q000633:toxicity
D000166:Acridines; D000485:Allergens; D000873:Anthracenes; D002733:Chlorophenols; D003374:Coumarins; D004136:Dinitrobenzenes; D012458:Salicylanilides; C020422:musk ambrette (artificial); C007713:fentichlor; C034020:anthracene; C018096:6-methylcoumarin