Sensitization to 2,4-dinitrochlorobenzene: influence of vehicle on absorption and lymph node activation.
Effective skin sensitization is dependent upon immune activation of lymph nodes draining the site of exposure. The influence of vehicle formulation on the vigour of lymph node cell proliferative responses to 2,4-dinitrochlorobenzene (DNCB) has been examined. Mice (BALB/c strain) were exposed topically to 0.5% DNCB dissolved in either acetone or propylene glycol (PG). A significantly greater lymph node cell proliferative response was induced by DNCB in acetone. The observed differences were not attributable to variations in the numbers of immunostimulatory dendritic cells accumulating in the draining nodes following sensitization. In parallel studies, the absorption and cutaneous disposition of DNCB dissolved in acetone or PG were measured in vitro using static diffusion cells and full thickness mouse skin. Although flux of DNCB through the skin was comparable with both vehicles over 24 h, the absorption of the allergen during the first 4 h of exposure was significantly faster when acetone was used as the vehicle. Localization of DNCB demonstrated that much less of the chemical allergen was present in the skin at 4 h when applied in PG vehicle. However, there were no measurable vehicle effects on skin disposition of DNCB at 24 h. These data indicate that the sensitization potential of DNCB is influenced significantly by the nature of the vehicle used, possibly due to consequential effects on chemical absorption and disposition. The studies described in this paper reveal that the application vehicle may have a significant influence on the ability of DNCB to induce immune activation of draining lymph nodes and hence skin sensitization and that this may in turn be associated with important changes in the absorption and/or disposition of the chemical within the skin.
Heylings
J R
JR
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Clowes
H M
HM
Cumberbatch
M
M
Dearman
R J
RJ
Fielding
I
I
Hilton
J
J
Kimber
I
I
D000096:Acetone / Q000737:chemistry; D000287:Administration, Topical; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects*
D004137:Dinitrochlorobenzene; D007509:Irritants; D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; D000096:Acetone; D019946:Propylene Glycol