title: Histological dermal changes caused by preparation and application procedures in percutaneous dose toxicity studies in dogs, rabbits and rats.
abstract: We reevaluated histological slides of dorsal skin in control animals from past percutaneous dose toxicity studies using dogs, rabbits and rats to provide background data concerning histological changes related to preparation and application procedures and vehicles or embrocations of every variety. Acanthosis, dermal or perifollicular inflammatory cell infiltration in dogs; hyperkeratosis, acanthosis, dermal inflammatory cell infiltration or hemorrhage in rabbits; and acanthosis, dermal inflammatory cell infiltration, crust or foreign body granuloma in rats were present as procedure-related underlying histological changes in the control animals. Four mechanical acts, (1) rubbing with gauze to remove an administered substance for reapplication, (2) use of a taut bandage to avoid slipping from the application site, (3) peeling a patch off as a preparation procedure for reapplication, and (4) clipping or shaving, were considered to cause injury to the skin. The degree of influence of the various application procedures was found to be as follows: sham, lotion < cream < ointment and tape in dogs; untreated control, sham < lotion < tape and poultice in rabbits; and sham, sodium carboxymethylcellulose < olive oil and lotion < ointment and tape in rats. The degree of ointment influence on rabbits is equivocal.
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Mitsuishi
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Oshikata
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Kumabe
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Katoku
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.affiliation: Kumamoto Laboratory, Nonclinical Research Center, LSI Medience Corporation, 1285 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Hamamura
authors.affiliation: Kashima Laboratory, Nonclinical Research Center, LSI Medience Corporation, 14-1 Sunayama, Kamisu-shi, Ibaraki 314-0255, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuchitani
keywords: acanthosis; dermal toxicity; dog; percutaneous dose toxicity; rabbit; rat