Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers

Abstract

Objectives: The aims of the study were threefold: to assess the skin uptake of the industrial catalyst dimethylethylamine (DMEA) (a) in vitro from water solutions by fresh guinea-pig and human skin specimens, (b) in gaseous form in vivo in human volunteers, and (c)␣to estimate the relevance of the uptake as an occupational hazard.

Methods: Specimens from the in vitro and in vivo experiments were analysed by gas chromatography using a nitrogen-sensitive detector.

Design: DMEA, diluted with water or isotonic saline solution was applied to fresh human or guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. Three healthy male volunteers each had their right forearm exposed (in a Plexiglass chamber) for 4 h to DMEA at each of three different levels (250, 500 and 1000 mg/m³ air). Urine was collected up to 24 h after the start of each experiment.

Results: DMEA penetrated both guinea-pig and human skin. The median steady-state flux and permeability coefficient (K _p) values, were 0.009 mg/cm² × h and 0.001 cm/h, respectively, for guinea-pig skin, and 0.017 mg/cm² × h and 0.003 cm/h, respectively, for human skin. The median uptake in the three volunteers at the different DMEA exposure levels (250, 500 or 1000 mg/m³) was 44, 64 and 88 μg, respectively. The median K _p for all experiments was 0.037 cm/h.

Conclusion: Uptake of DMEA through the skin is of far less importance than simultaneous uptake via the airways. Thus, the amount of DMEA excreted in urine is a variable of limited use for the purposes of biological monitoring. Although a wide range of K _p values was obtained in the in vitro experiments, both for guinea-pig and human skin, there was no marked difference in median K _p values between the two types of skin. The K _p values were lower than those obtained for human forearm skin in vivo. However, future studies of other tertiary aliphatic amines may show the in vitro␣method to yield values predictive of those obtained in in vivo studies.