Dermal toxicity studies: factors impacting study interpretation and outcome.
The field of dermal toxicity continues to evolve in order to accurately predict dermal (and systemic) responses in humans to topically applied chemicals. Although the testing methods have undergone extensive refinements, idiosyncrasies and unexpected issues during the conduct of these studies are not unusual due to the plethora of new vehicles available for formulating test substances, changing regulatory requirements, and introducting new strain and/or species of laboratory animals as no single species or method seems to suffice for evaluating skin toxicity. The objective of this article is to illustrate some pragmatic issues that should be considered during the conduct as well as interpretation of dermal toxicity studies. Routine procedure-related issues such as hair clipping, tape stripping, and wrapping the animal's torso to prevent oral ingestion can influence the interpretation. Excipients used in dermal toxicity studies may be nontoxic when used alone but complex dermal formulations can result in unexpected irritation and toxicity. In conclusion, interpretation and risk assessment of dermal toxicity studies should be done in a comprehensive manner, taking into account procedure-related impact on study results, unique species susceptibility, limitation of gross visual (naked eye) observation for evidence of toxicity, and normal anatomical variation.
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA sundeep.a.chandra@gsk.com.
Sundeep A
SA
Chandra
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Alan H
AH
Stokes
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Rick
R
Hailey
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Christine L
CL
Merrill
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
David H
DH
Melich
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Kristina
K
DeSmet
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Sylvia M
SM
Furst
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Richard A
RA
Peterson
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Katherine
K
Mellon-Kusibab
Safety Assessment, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Rick R
RR
Adler
D000287:Administration, Topical; D000818:Animals; D012867:Skin / Q000187:drug effects*; D012871:Skin Diseases / Q000139:chemically induced*; D012882:Skin Tests / Q000379:methods* / Q000592:standards; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
Draize; cutaneous; dermatitis; experimental procedure; irritation; minipigs; rabbits; rats; sensitization; skin; topical; toxicity; vehicle