Evaluation of modified methods for determining skin irritation.

The premarket testing of household cleaning products for dermal irritancy is best achieved via human testing. Animal dermal irritation testing is generally limited to screening for possible dermal hazard of totally new or unique products or ingredients prior to human testing or to meeting regulatory requirements of government bodies. Alternatives to animal tests are being sought; however, until such time that these alternatives are identified, validated, and accepted by government bodies, the judicious use of animal testing remains a necessity. Modifications to standard animal skin irritation test procedures have been evaluated against human skin irritation results with the objective of defining one method that could be used in place of current standard procedures that differ slightly from one another, and thereby avoid excessive and redundant use of animals. Hill Top Chambers (19 mm) and standard gauze patches (U.S. Department of Transportation procedure) were used to obtain comparative irritation responses for 24 cleaning products, common caustics, and acids in rabbits and humans. Exposure times were 1 or 4 hr, and responses were graded over a 72-hr period. Results indicate that use of the Chamber offers the potential to (1) reduce the number of animals used for skin irritation screening (smaller group size and up to eight test substances/concentrations per animal); (2) eliminate the need for conducting multiple tests to satisfy different governmental requirements; and (3) reduce animal stress by reducing exposure times without compromising the value of the irritancy patch test as a screening tool. When animal data are required, it is suggested that the use of a Chamber and other modifications of traditional test procedures offers advantages that could result in using fewer animals and/or have less potential for producing unnecessarily severe responses in animals.

Synthesis and antitumor activity of some aromatic seleno lactones.

Several aromatic seleno lactones have been synthesized and shown to possess significant inhibitory activity against human colon tumor-8r cells in culture at concentrations lower than 1 mM. Although all of the compounds tested were found to be active, 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarinoctanoate (3d) and 5-hydroxy-3-[(phenylseleno)methyl]hydrocoumarindecanoate (3e) were found to be the most effective in inhibiting cell growth. In situ formation of the corresponding alpha-methylene lactones is postulated to account for the cytotoxic activity in this class of compounds.