In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.
Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly.
Zorin
S
S
Pharmacia & Upjohn, Helsingborg, Sweden.
Kuylenstierna
F
F
Thulin
H
H
D004353:Drug Evaluation, Preclinical; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D017575:Gloves, Protective / Q000592:standards; D006801:Humans; D009538:Nicotine / Q000493:pharmacokinetics* / Q000506:poisoning*; D017711:Nonlinear Dynamics; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis / Q000517:prevention & control; D010539:Permeability; D012869:Skin Absorption / Q000187:drug effects*; D012996:Solutions; D013997:Time Factors
D012996:Solutions; D009538:Nicotine