Effects of arsenic on human keratinocytes: morphological, physiological, and precursor incorporation studies

Measurement of in vitro percutaneous absorption of As(III) and As(V) by artificial human skin shows a strong affinity of arsenic for the human keratinocytes, with 1-10% of the applied arsenic dose retained by the artificial skin per hour. The inordinate retention of arsenic by the skin is a risk factor for As toxicity. The calculated permeability constant (K(p)) averaged about 4.3 x 10(-5) cm/h for As(V) and 10.1 x 10(-5) cm/h for As(III). A facile calculation suggests that dermal absorption during showering and hand washing can be an important exposure route if the water contains more than 100 microg/L As(III) or As(V). The effects of the absorbed arsenic in artificial skin were evaluated in terms of morphological characteristics, integrity of the cell membrane (by means of lactate dehydrogenase and MTS assays), and rates of DNA, RNA, and protein synthesis estimated by incorporation of radioactive precursors. We found significant morphological changes, cytotoxicity associated with disruption of the cell membrane, and inhibition of DNA and protein syntheses at As(III) exposure doses as low as 10 microg/L.