Certain types of plastic materials require the addition of appreciable quantities of plasticizers to impart specific physical-chemical properties to the final item. Presently, many vinyl devices used with drug products may contain plasticizers of the phthalate type. For this reason, a series of phthalic acid esters were evaluated for parenteral toxicity including LDba values and hexobarbital narcosis. Experiments utilized in the study also included i.p. injections in mice for acute toxicity profiles, i.v. administration in rabbits for blood pressure and respiration effects, and intradermal injections into rabbits for irritation effects. A further study was conducted to note what effects repeated i.p. doses of the phthalates would have o n mice over a period of time, examining the effects o n organs, weight gain, and the blood. Finally, tissue culture experiments were conducted to attempt to correlate certain of the toxicity manifestations. The most salient feature of the toxicity of these compounds was the central depression o n the animals and the rather low order of toxicity by the parenteral route of administration.
plastic materials (e.g., polyvinyl preciable quantity of plasticizers to impart specific physicocheniical and mechanical properties. In medical practice, these materials are used as h a p , tubings, vehicles for administration, and coYe4on or storage devices. A high degree of safe+.y must be established and maintained in orJcr to prevent any adverse effect when and if an iqredient from the plastic device migrates into a parenterally administered product. Previous reports from this laboratory have indicated that ccrtain plastic devices used rnedically can release one or more ingredients into tissue or solvent systems (1-3). Furthermore, these "migrated" ingredients, when in sufficient concentrations, can elicit definite pharmacological responses. One study by Guess, Autian, and Meyers (4) demonstrated that a group of citric acid esters used as plasticizers for vinyl formulations produced definite toxicological effects when administercd by parenteral routes. These same compounds, 1iou.ever, were extremely safe even in large quantities when administered orally to animals. Presently, orieof theiriostcominonlyused jiroups of plasticizers is the phthalic acid esters. These and related compounds generally have low volatility (j), low water solubility ((i). some degree of absorption through the skin, and toxicity when takcn into the body by the inhalation of vapors or by the oral ronte (7-0). Little information, however, is available as to the degree of toxicity or modes of actions of the phthalic acid estcrs when they arc introduced parenterally (10, 11). This paper reports a series of biological experiments in which 8 of the esters were evaluated as C""' "IN chloride) require the introduction of an a p -~~ -~