Teratogenicity of Phthalate Esters in Rats

In the past, it was demonstrated that small quantities of phthalates may be released from polyvinyl chloride items to physiological solutions. To ascertain the effect these plasticizers might have upon the fetus, a teratogenic study was undertaken in rats using eight phthalate esters. Six of the phthalates, whose acute intraperitoneal LD50 values were below 10 ml./kg., were administered to rats at doses representing one-tenth, one-fifth, and one-third of the acute LD50 dose on the 5th, 10th, and 15th day of gestation; the two less toxic compounds were injected at levels of 5 and 10 ml./kg. Distilled water and normal saline were tested at 10 ml./kg., and cottonseed oil was tested at 5 and 10 ml./kg. Untreated animals were used for control values. The number of corpora lutea ranged from 52 to 65 per group of five rats, with no apparent distribution according to treatment. Embryo-fetal toxicity ranged from 0% to a high of 98.2%. Fetal malformations ranged from 0 to 100%, both for gross and skeletal abnormalities, with skeletal defects generally being more common. Fetuses from all phthalate-treated groups were smaller (p ≤ 0.01) than the untreated controls. Absence of tail, anophthalmia, and twisted hind legs were the most common gross abnormalities, while elongated and fused ribs and abnormal skull bones were the most common deformities found in stained skeletal specimens.