Dermal absorption of neat liquid solvents on brief exposures in volunteers.

The dermal absorption of liquid 1,1,1-trichloroethane (111TRI), trichloroethene (TRI), tetrachloroethene (TETRA), toluene (TOL), and m-xylene (XYL) was studied in volunteers. The solvents were applied for 3 min on the volar forearm over an area of 27 cm2. An inhalation exposure with a known input rate served as a reference exposure. Using the linear system dynamics method, permeation rates were calculated from exhaled air concentration courses measured after both inhalation and dermal exposure. The permeation time courses of the solvents showed two different patterns. TRI, TOL, and 111TRI in three subjects showed fast increase in permeation, reaching maximal permeation rates a few minutes after initiation of exposure. Slower permeation was seen in the other three subjects exposed to 111TRI and in all subjects exposed to TETRA and XYL with the time of maximal permeation rates of 15-25 min. These differences in the permeation may partly be explained by the irritation of the skin observed in all subjects showing fast permeation kinetics. The flux into the skin averaged over the exposure period amounted to 56, 430, 69, 223, and 46 nmol/cm2/min for 111TRI, TRI, TETRA, TOL, and XYL, respectively. Comparing the dermal uptake with the respiratory uptake at the TLV, all solvents showed substantial skin absorption, although at present only TOL has a skin indication in the American Conference of Governmental Industrial Hygienists threshold limit value list.

Cytotoxicity of retinoic acid, menadione and aflatoxin B(1) in rat liver slices using Netwell inserts as a new culture system.

Precision-cut rat liver slices were used to develop a new dynamic incubation system in which histomorphology and measurement of the release of lactate dehydrogenase (LDH) and the conversion of MTT were applied to evaluate cytotoxicity. Liver slices, precision-cut using a Krumdieck tissue slicer, were cultured in a new system using 200-mum polyester mesh Netwell inserts in six-well cell-culture clusters on a rocker platform at 37 degrees C and 40% O(2). The major advantage of this new culture system is the easy way in which slices can be manipulated and the culture medium be sampled or changed. Rat liver slices were exposed for 4 hr to retinoic acid (RA), menadione or aflatoxin B(1) (AFB(1)). Directly after treatment and after an additional 20-hr recovery period, histomorphological observations of slices were made, and LDH release and MTT conversion were measured. Slices exposed to RA showed dose-related cytotoxicity in the MTT assay only. The cytotoxic response to AFB(1) was more pronounced in the assay of LDH release than in the MTT assay. Histomorphology, LDH release and the MTT assay revealed cytotoxic effects induced by menadione. We conclude that culturing liver slices using Netwell inserts is a good alternative to other culture systems for testing non-volatile compounds.