Phthalate ester toxicity in human cell cultures

Abstract

Di-2-ethylhexyl phthalate and butyl glycolyl butyl phthalate, plasticizers which can be leached into blood from polyvinyl chloride-containing medical devices, cause significant growth inhibition in cultures of the human diploid cell strain WI-38. The ID50 (dose which causes 50% growth inhibition in tissue culture) values for di-2-ethylhexyl phthalate and butyl glycolyl butyl phthalate were 70 [mu] and 12 [mu], respectively, for WI-38 cells. Toxic effects were greater in a replicating cell population than in a nonreplicating, confluent cell layer. WI-38 cells which were grown in 160 [mu] di-2-ethylhexyl phthalate for 3 days, and subsequently subcultured into control medium, showed only 60% of control growth after 5 days in control medium. Cells treated with 14 [mu] butyl glycolyl butyl phthalate for 3 or 5 days exhibited growth equivalent to the controls when subcultured into control medium. Toxic levels for di-2-ethylhexyl phthalate were within the range of concentrations found in blood which has been stored in polyvinyl chloride blood bags for up to 21 days at 4[deg]C. ID50 values were reported for several other phthalate esters and for two nonphthalide compounds which are leachable from certain polyvinyl chloride plastic medical devices.