The teratogenic potential of alkoxy acids in post-implantation rat embryo culture: structure-activity relationships

Alkoxy acids are the active metabolites of teratogenic glycol ethers. To examine the relationship of chemical structure to embryotoxicity, the effects of 6 acids on the development of 9.5-day rat embryos over 48 h in culture were studied. Methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) (5 mM) were growth-retarding and induced gross structural defects, with MAA being more effective. n-Propoxyacetic acid (n-PAA) and n-butoxyacetic acid (n-BAA) (5 mM) were markedly less embryotoxic and produced only minor anomalies. Thus, the activities of these substituted acetic acids decreased with the increase in the length of the alkoxy chain. 3-Methoxypropionic acid (3-MPA) and 4-methoxybutyric acid (4-MBA) (5 mM) were much less active than MAA and induced only minor defects. Therefore in this series: RO(CH2)nCOOH, an increase in the value of n caused a greater reduction in embryotoxicity than did an increase in chain length of the alkyl group R.