Biomedical subjects
Publications and source records attributed to J Autian.
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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.
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A series of poly(methyl methacrylate) formulations differing widely in chemical and physical properties was employed for the evaluation of primary screening methods for the assessment of acute toxicity. Materials and USP extracts of materials were tested in parallel. Tissue culture, hemolysis, intradermal irritation, systemic toxicity, muscle implant and histopathologic responses were determined for each of 27 formulations. A determination of the nonvolatile methanol extractable components was carried out on each formulation. The formulations varied with respect to percent, w/w, methyl methacrylate, N,N-dimethyl-p-toluidine, stannous octoate, 3, 4-diamino-toluene and, also, with respect to curing conditions. Volatile components, primarily methyl methacrylate, of three selected formulations were determined quantitatively by vacuum distillation and mass spectrographic analysis. Statistical analysis of the primary data indicated a significant correlation of residue weight (methanol extractable) with hemolytic activity (r = 0.93) and with the cumulative biological response (r = 0.9). Multiple linear regression analysis of residue weights with hemolysis and intradermal irriation responses gave the highest overall correlation (r = 0.96). Hemolytic activity and tissue culture responses were significantly correlated (r = 0.87). It was concluded that the observed variation of biological test results reflected significant differences in the toxicity of the test materials. The poly(methyl methacrylate) series examined was relatively low in toxicity and the biological tests examined, particularly the in vitro tests, were found to be responsive to formulation and curing conditions which indicated their suitability for primary toxicity screening.
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.
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.
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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.
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.
A series of systemic toxicity tests for various types of compounds are presented with illustrative data and discussed in regard to their relevance as potential screening tests for dental compounds and products. In developing and marketing a new dental material, it is important not only to ensure safety for the patient but also for the dentist, dental assistant, and laboratory worker who routinely handles and uses the product. Data are presented on a number of commercially available dental products as well as various chemical entities, which were tested by one or more of the methods described.
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