The Use of Mechanistically Defined Chemical Mixtures (MDCM) to Assess Component Effects on the Percutaneous Absorption and Cutaneous Disposition of Topically Exposed Chemicals.

Quantitating the Percutaneous Absorption of Mechanistically-Defined Chemical Mixtures

“…For naphthalene, the additive package which transforms JP-8 into JP-8(100) seemed to have increased its penetration. These findings are not totally unexpected, since we have reported on similar complex interactions when absorption of various organics (parathion, carbaryl, benzidine) was studied from defined chemical mixtures Qiao et al, 1996;. Possible interactions include chemical binding, chemical effects from surfactants, stratum corneum lipid interactions from enhancers, solventmediated lipid extraction, low level irritation, and vasomodulation.…”

“…This method combines the advantages of the star plot and of the analysis of means (ANOM); we call it the compass plot. The name "compass plot" was first introduced for the presentation of the results of a chemical mixtures experiment (Qiao, 1996). However, in that paper compass plots were used only as a descriptive tool.…”

“…To determine a constituent effect, we studied the absorption, penetration, and cutaneous distribution of these marker compounds in the in vitro isolated perfused porcine skin flap (IPPSF) when dosed from Jet-A, . This model system has been successfully utilized to model the mechanism of percutaneous chemical absorption Riviere et al, 1995b;Qiao et al, 1996) and to extrapolate these results to humans Wester et al, 1998;Williams et al, 1990). We also assessed the absorption of naphthalene and dodecane from a fraction of a so-called aged JP-8 "puddle" which was produced by allowing JP-8 to evaporate from an open glass petri dish left in a fume hood for 24 h. After the more volatile components evaporated, the remaining mixture should resemble residual jet fuel remaining 24 h after a jet fuel spill.…”

“…There is a 2 3 factorial experiment in each vehicle (Qiao, 1996). To access the risk of cutaneous exposure to chemical mixtures, acetone or dimethylsulfoxide (DMSO) was used as a vehicle.…”

Pesticides and Human Health

“…The increased in nitroreductase activity may account for lindane-parathion interaction and could influence the metabolism, toxicity and risk assessment of many other environmental nitrocompounds that become toxic, mutagenic or carcinogenic upon reduction of their nitro-groups. Also, the chemical components in topically exposed mixtures may have significant effects on the prepenetration fate, penetration/distribution pattern, metabolism and precutaneous profile of parathion/drug in the mixture (Qiao et al, 1996). Therefore, multiple level interactive effects on parathion absorption must be considered into any effort to identify critical mechanisms that affect assessment of topically exposed mixtures.…”