Evaluation of barrier creams against sulphur mustard: (II) In vivo and in vitro studies using the domestic white pig.
Previous studies in our laboratory have demonstrated that barrier creams, comprising perfluorinated polymers, are effective against the chemical warfare agent sulphur mustard (SM) when evaluated using human skin in vitro. The purpose of this follow-up study was to further evaluate three candidate (perfluorinated) barrier creams against SM (vapour) using the domestic white pig. The severity and progression of the resulting skin lesions were quantified daily for three weeks post-exposure using biophysical measurements of transepidermal water loss (TEWL) and skin reflectance spectroscopy (SRS). Skin biopsies obtained post-mortem were evaluated by light microscopy and additional skin samples were obtained from adjacent (unexposed) skin sites for a comparative in vitro skin absorption study. Samples of SM vapour within the dosing chambers were measured ex vivo to ascertain the exposure dose (Ct). The three creams were highly effective against SM in vivo (Ct approximately 5000 mg.min.m(-3)): After 3 weeks, barrier cream pre-treated sites were not significantly different from control (unexposed) skin when evaluated by TEWL, SRS or histology. In contrast, skin exposed to SM without pre-treatment showed evidence of persistent damage that was consistent with the slow healing time observed in humans. The amount of SM absorbed in vitro in untreated pig skin was similar to that required to cause comparable lesions in human skin (8-20 and 4-10 microg.cm(-2), respectively), further validating the use of pigs as a toxicologically-relevant dermal model for SM exposure.
Chemical Hazards and Poisons Division, Health Protection Agency, Chilton, Didcot, Oxfordshire, United Kingdom. Rob.chilcott@hpa.org.uk
Robert P
RP
Chilcott
Christopher H
CH
Dalton
Zoe
Z
Ashley
Ceri E
CE
Allen
Simon T
ST
Bradley
Michael P
MP
Maidment
John
J
Jenner
Roger F R
RF
Brown
Robert J
RJ
Gwyther
Paul
P
Rice
D000279:Administration, Cutaneous; D000818:Animals; D002619:Chemical Warfare Agents / Q000378:metabolism / Q000633:toxicity*; D015194:Diffusion Chambers, Culture; D004643:Emollients / Q000008:administration & dosage*; D004890:Erythema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005465:Fluorocarbon Polymers / Q000008:administration & dosage*; D009151:Mustard Gas / Q000378:metabolism / Q000633:toxicity*; D009824:Ointments; D015203:Reproducibility of Results; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects; D034421:Sus scrofa; D013997:Time Factors; D014870:Water Loss, Insensible / Q000187:drug effects
D002619:Chemical Warfare Agents; D004643:Emollients; D005465:Fluorocarbon Polymers; D009824:Ointments; D009151:Mustard Gas