The developmental toxicity for each of 45 carboxylic acids was determined for Xenopus embryos. Acids tested included 12 unbranched, saturated aliphatics, 12 branched, saturated aliphatics, 12 unsaturated aliphatics, and 9 aromatics. Embryos were collected following hormone-induced breeding and exposed to at least eight concentrations of the acid, along with a control. For each concentration, 25 properly developing embryos were exposed to the acid solution for 96 h. Each acid was tested on at least three separate occasions and the data were pooled to calculate 96-h LC50 (lethality), 96-h EC50 (malformation), and DHI (developmental hazard index = 96-h LC50/96-h EC50) values. The endpoint data were subjected to quantitative structure-activity relationship (QSAR) analyse: and computer-automated structure evaluation (CASE). Variation in acid-induced lethality was effectively explained by partitioning and ionizability of the acids, while partitioning alone was somewhat effective in explaining variation for acid-induced malformation. The results indicated that developmental hazard of the acids to Xenopus embryos is primarily dependent on carbon-chain length, with acids containing five carbon atoms in the chain tending to be the most potent. Unsaturation reduced the hazard in comparison with the corresponding unbranched saturated acid. Developmental hazard was highest for 2-position branched compounds with a 5- or 6-C chain, but was reduced for 2-position branched acids with a 3- or 4-C chain. Hazard of the non-2 position branched acids was variable. Valproic (2-propylpentanoic) acid showed the highest developmental hazard with Xenopus, twice that of any other acid tested.
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