Carcinogenic activity of a chlorinated polyether polyurethan.

On the basis of the results of an earlier study, a particular polyurethan sample (Y-238) was selected for further evaluation of its carcinogenic potential. This sample was subjected to physical and chemical tests for elucidation of its chemical structure, molecular weight, and molecular weight distribution. Additional biological tests were conducted on male NBR rats by implanting various quantities of the sample i.p., while others received an intrabronchus implant. Tumors, assessed histologically as malignant, were observed following both routes of implantation. The most common neoplasms of the pulmonary site was epidermoid carcinoma, while fibrosarcoma was the most common neoplasm in the peritoneal cavity. Data from the i.p. implantation suggested a dose-related incidence of cancers.

Carcinogenesis from polyurethans.

Seventeen polyurethans, containing various substituent groups, and a polyethylene were implanted i.p. in groups of male black Bethesda rats and were evaluated for carcinogenesis over a 2-year period. Thirteen of the polyurethans and the polyethylene were similarly studied in females. Tumor development in these animals was expressed in terms of the incidence in the at-risk population, and the tumorigenic latent period was approximated for each sample. Twenty months after implantation, the relative tumorigenicity (area under the corrected cumulative tumor mortality versus time curve) in the males ranged from 0 (for the unimplanted controls) to 6.18 (for Y-238); for female rats this range was 0.29 (for unimplanted controls) to 5.72 (for Y-238). Estimated latent periods in the males ranged from 5 months (for Y-304) to 16 months (for Y-303), and 22.5 months for the unimplanted controls; for the females, the range was from 9 months (for Y-290) to 13.5 months (for Y-217), and 14 months for the unimplanted controls. The relative tumorigenicity of each sample was also compared to its in vitro activation energy for thermal decomposition. These data are discussed in terms of solid-state versus chemical carcinogenesis.

Structure-toxicity relationships of acrylic monomers.

Esters of acrylic acid, in particular methyl methacrylate, have wide applications in a number of industrial and consumer products, forming very desirable nonbreakable glass-like materials. In dentistry, the monomers are used to prepare dentures and a variety of filling and coating materials for the teeth. Surgeons utilize the monomers to prepare a cement which helps anchor prosthetic devices to bone. Special types of acrylic monomers such as the cyano derivatives have found a useful application as adhesive materials. Most of the acrylic acid esters are volatile substances and can produce various levels of toxicity if inhaled. A large number of workers thus exposed to the vapors of these esters can develop clinical symptoms and signs of toxicity. This paper will discuss the toxicity of a large number of acrylic esters, and will attempt to show structure-activity relationships where such data are available. General comments will also be made as to the potential health hazards this variety of esters may present to selected segments of the population.

Antifertility effects and dominant lethal assays for mutagenic effects of DEHP.

Results of past animal studies have indicated the antifertility effects of phthalate esters and additional studies have suggested the potential mutagenic effects at very high doses. A toxicity study in mice has also been conducted in which chronic LD50 values were calculated for a group of phthalate esters. For DEHP, for example, the acute LD50 was 38.35 ml/kg, but after 10 weeks the value fell to 1.37 ml/kg, suggesting that the ester was producing a cumulative toxicity agent even at lower doses in regard to antifertility and mutagenic effects in mice. Preliminary results indicated that antifertility effects occurred with as little as three subcutaneous doses of 1 ml/kg each. Calculations of mutagenic index revealed a dose-dependent effect but no stoichiometric relationship was established.

Correlation of kinetic parameters and thermal behavior of segmented polyurethane elastomers with biological responses.

Kinetic studies of thermal degradation of 16 segmented polyether polyurethane samples, containing various amounts of 3,4-diaminotoluene and dibutyltin diacetate as additives, were carried out by thermogravimetry. From a single dynamic thermogravimetric experiment, the temperatures of initiation of degradation, 10, 25, and 50% (w/w) of degradation, as well as the activation energies for degradation, were determined. The activation energies were computed from the thermogravimetric curves using Broido's graphical approximation method, which applies to first-order decomposition kinetics. The results of stepwise multiple linear regression analysis indicate that the biological responses to elastomar samples, such as tissue culture, hemolysis, intramuscular implant, intradermal irritation, systemic toxicity, and histopathological rating, and the cumulative biological response index are highly correlated with thermal stability and kinetic measurements of the materials.

Maternal-fetal transfer of 14C-di-2-ethylhexyl phthalate and 14C-diethyl phthalate in rats.

14C-Di-2-ethylhexyl and 14C-diethyl phthalates were administered intraperitoneally to pregnant rats on either Day 5 or 10 of gestation. Rats were sacrificed at 24-hr intervals starting on Days 8 and 11, respectively; maternal blood, fetal tissue, amniotic fluid, and placentas (whenever possible) were obtained. The 14C-activity of each sample was determined by scintillation counting. It was found that both diesters and/or their metabolic products were present in each of these compartments throughout the gestation period, thus suggesting that the embryo-fetal toxicity and teratogenesis reported previously could be the results of a direct effect of the compound (or its metabolites) upon developing embryonic tissue. Additionally, the reduction in concentration of 14C from these tissues as a function of time was found to fit a first-order excretion curve. From this model curve, the half-life for both compounds was calculated; the average was about 2.33 days for di-2-ethylhexyl phthalate and 2.22 days for diethyl phthalate.