Guinea pig maximization test assessment of hydrocortisone and tixocortol pivalate.
The anti-inflammatory properties of topical corticosteroids are well documented; additionally, their sensitization potential is also known. We aimed to assess the relative sensitization potential of hydrocortisone and tixocortol pivalate in an animal assay as it relates to potential for sensitization in humans. Using the guinea pig maximization test (GPMT), animals were sensitized intradermally on d0, and again topically on d7. On d21 the animals were challenged topically with a closed patch for 24 h and readings were taken 24 h and 48 h post-challenge. A sham control group received the same induction and challenge applications excluding the test agent. Animals were subsequently rechallenged with open application; the tixocortol pivalate group was further retested at different test agent concentrations to determine threshold concentration that elicited response. Tixocortol pivalate resulted in sensitization rates of 42% (24 h) and 80% (48 h); hydrocortisone exhibited 0% (24 h) and 5% (48 h). Scores ranged from 0% (sham group) to 2.4 (48 h tixocortol pivalate). Open rechallenge also resulted in greater tixocortol pivalate sensitization rates compared to hydrocortisone, 82% verse 16% at 48 h, respectively. All tested concentrations of tixocortol pivalate induced sensitization, albeit at differing rates dependant on concentration and timepoint. We conclude that the GPMT remains largely for hazard identification, as it was originally designed, and requires further data sets regarding quantitative induction and elicitation for risk assessment of various compounds in clinical implications.
TRG Inflammation/Immunology, Bayer Schering Pharma AG, Berlin, Germany. pmirshahpanah@gmail.com
Parham
P
Mirshahpanah
Howard I
HI
Maibach
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000009:adverse effects* / Q000031:analogs & derivatives*; D012867:Skin / Q000187:drug effects; D012882:Skin Tests / Q000379:methods
D000485:Allergens; D000893:Anti-Inflammatory Agents; C019112:tixocortol pivalate; D006854:Hydrocortisone