Safety prediction of topically exposed biocides using permeability coefficients and the desquamation rate at the stratum corneum

J Toxicol Sci. 2014 Jun;39(3):475-85. doi: 10.2131/jts.39.475.

Abstract

Advances in the synthesis and utilization of new chemical compounds have led to improvements in our daily lives. However, new chemicals may be both beneficial and toxic. Thus, exposure to these new compounds should be restricted in an attempt to limit their potential toxicities. We predicted the safety of three biocides (p-cresol, diazinon and resmethrin) by comparing their skin permeability coefficients and desquamation rate (the counter flux of permeability coefficient for chemical compounds induced by skin turnover) following skin exposure. In vitro skin permeation experiments revealed that the permeability coefficients of diazinon and resmethrin were smaller than the desquamation rate; therefore, these biocides could not permeate the skin, which resulted in very low skin concentrations of these compounds. On the other hand, the skin concentration of p-cresol was high because of its higher permeability coefficient than the desquamation rate. Furthermore, low in vitro cell viability was reported for skin exposed to p-cresol. These results in the present study indicate that the method described herein is useful for predicting the toxicities of chemicals following their topical exposure.

MeSH terms

  • Administration, Topical
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cresols / administration & dosage
  • Cresols / pharmacokinetics*
  • Cresols / toxicity*
  • Diazinon / administration & dosage
  • Diazinon / pharmacokinetics*
  • Diazinon / toxicity*
  • Disinfectants / administration & dosage
  • Disinfectants / pharmacokinetics*
  • Disinfectants / toxicity*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Permeability / drug effects*
  • Pyrethrins / administration & dosage
  • Pyrethrins / pharmacokinetics*
  • Pyrethrins / toxicity*
  • Rabbits
  • Rats
  • Rats, Wistar
  • Skin / cytology
  • Skin / metabolism*

Substances

  • Cresols
  • Disinfectants
  • Pyrethrins
  • 4-cresol
  • Diazinon
  • resmethrin