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High-density cultures of mouse embryo limb bud cells differentiate and synthesize an extracellular matrix containing sulfated proteoglycans. Since these in vitro events are related to those that occur during fetal development, we have investigated the use of cultured limb bud cells for the analysis of the activities of chemical teratogens. We have established the conditions for the use of the radiochemicals 35SO=4 and 3H-thymidine for the assessment of chemical effects on sulfated proteoglycan and DNA synthesis, respectively, in mouse limb bud cells. By performing double-labeling experiments in the presence of test chemicals, the preferential inhibition of either proteoglycan synthesis or DNA synthesis could be demonstrated for 19 of 22 known mouse teratogens tested. The five nonteratogens tested did not cause significant differences in the inhibition of either macromolecular class. The overall predictive accuracy of the system was approximately 89%, and the false-negative rate was approximately 14.8%. No false positives were observed. These data showed that this cell culture system differentiated between the activities of a limited set of selected mouse teratogens and nonteratogens, suggesting that cultured mouse embryo limb bud cells may constitute the basis for the development of a powerful tool for analyses of chemical teratogenic potential.

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Eight phthalate esters, with alcohol chain lengths of 1–11 carbon atoms and with various degrees of branching, were tested in vitro in the L5178Y mouse lymphoma mammalian cell mutation assay and in the Balb/3T3 cell transformation assay. The tests were performed as part of a voluntary testing agreement between the Chemical Manufacturers Association’s Phthalate Esters Panel and the United States Environmental Protection Agency (US EPA). The esters tested were: dimethyl phthalate (DMP), di‐n‐butyl phthalate (DBP), butyl benzyl phthalate (BBP), di‐{n‐hexyl, n‐octyl, n‐decyl} phthalate (610P), di‐isononyl phthalate (DINP), di‐{heptyl, nonyl, undecyl} phthalate (711P), di‐isodecyl phthalate (DIDP) and di‐undecyl phthalate (DUP). Both DMP and DBP were found to produce significant increases in the mutant frequency in the mouse lymphoma assay in the presence but not in the absence of an Aroclor‐induced rat liver activation system (S‐9). Ester 610P gave equivocal results in the mouse lymphoma assay in the presence and absence of rat liver S‐9. There was no indication of mutagenic potential for any of the other test materials in the mouse lymphoma assay, and none of the test materials increased transformation frequency in the Balb/3T3 cell transformation assay. Aldehyde metabolites of the de‐esterified alcohols are postulated to play a role in the positive results for DMP and DBP. Copyright © 2000 John Wiley & Sons, Ltd.

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