Developmental toxicity of phtalates. Read accross approach

Phthalates are diesters of the ortho phthalic acid. They are extensively used as plasticizers, primarily for polyvinyl chloride (PVC), and as solvents. They are present in a large variety of consumer products and widespread exposure to multiple phthalates has been documented in the general population.
Although they constitute a chemical class, all phthalates do not exhibit the same toxicological properties in experimental animal studies. A specific pattern of toxicity have been predominantly associated with the category of transitional phthalates, delineated by a linear portion (backbone) of 4 to 6 carbons in the ester side chains. Of most concern, they produce similar severe reproductive and prenatal toxic effects. The fetal testis is their primary target after in utero exposure.
Our aim was to evaluate the developmental toxic potential of eleven phthalates for which few or no information was available. They included: two phthalates belonging to the low molecular weight category and having a C3 backbone, one transitional phthalate with a linear C6 side chain, five linear or branched phthalates from the high molecular weight phthalates category ( C7 backbone), and three phthalates with carbon side chains deviating from the common structural features (i.e. alkyl esters with double bond, saturated C6 cycle, or ether group). Each substance was administered to pregnant rats, by gavage, at doses generally ranging from 0.1-0.25 to 1 g/kg/day.
Our studies showed that diisobutyl (branched side chain with a C3 backbone), di-n-hexyl (C6 backbone), and diisooctyl (mixture of isomers, some of them with C4-C6 backbones) phthalates had teratogenic and embryoletal properties, and severely impaired the development of the male reproductive system. Toxicity profiles of diallyl and dimethoxyethyl phthalates, which possess atypical molecular configurations (double bond and ether, respectively), were unique compared to other phthalates. Increase in the number of examined phthalate analogues provided greater confidence in the category and read-across approaches for these substances, especially for the complex phthalates and/or not within the C4-C6 category.