Structure-activity relationships for osteolathyrism: II. Effects of alkyl-substituted acid hydrazides

A series of 8 alkyl-substituted acid hydrazides were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Each acid hydrazide was able to induce the connective tissue defect osteolathyrism. The 96-h toxicity (log LC50) and 96-h teratogenicity (log EC50) endpoints are correlated with hydrophobicity measured by the fragment substitution constant (Fr). These relationships suggest the rate limiting step is the ability of the chemical to reach the site of action. However, the teratogenic index (LC50/EC50) is negatively correlated with molar refractivity (MR), a substituent corrected molar volume term. This latter relationship suggests steric hindrance.