Estimation of the percutaneous absorption of permethrin in humans using the parallelogram method

The objective of this study was to develop an estimate of the percent dermal absorption of permethrin in humans to provide more accurate estimates of potential systemically absorbed dose associated with dermal exposure scenarios. Piperonyl butoxide (PBO) was used as a reference compound. The human percutaneous absorption estimate was based on the assumption that the ratio of in vivo dermal absorption (expressed as a percentage during a given time period) of permethrin through rat skin to in vitro dermal absorption through rat skin was the same as the ratio of in vivo dermal absorption in humans to in vitro dermal absorption with human skin, known as the parallelogram method. The ratio of dermal absorption by in vitro rat skin to absorption by in vitro human skin ranged from 6.7 to 15.4 (for a 24-h exposure period) with an average of 11. Data suggest in vivo human dermal absorption values for permethrin ranging from 1.4 to 3.3% when estimated based on 24-h in vivo rat values, and 2.5 to 5.7% based on 5-d in vivo rat values. The parallelogram method used to estimate dermal absorption of permethrin and PBO is supported by results from several other compounds for which in vivo and in vitro rat and human dermal absorption data exist. Collectively, these data indicate that estimating human dermal absorption from in vitro human and rat plus in vivo rat data are typically accurate within ±3-fold of the values measured in human subjects.