Poly(anhydrides) proposed for use as vehicles for controlled drug delivery were administered subcutaneously in Sprague-Dawley rats at two dosage levels (800 mg/kg rat and 2400 mg/kg rat) for a period of eight weeks. Biocompatibility was assessed using a number of methods. Thirty-six clinical chemistry and hematology parameters were monitored throughout the study. Blood values were statistically analyzed for any possible effects due to the implanted polymer. After 8 weeks, rats were sacrificed and complete necropsies were performed. Histological evaluations of 33 organ sites including heart, lung, liver, kidney, and brain were performed. In addition, subcutaneous implant sites were excised and examined both grossly and microscopically. Results from evaluations of blood chemistry and hematology data, organ analyses and local implant site analyses overall demonstrated that the poly(anhydride) biomaterial possessed excellent in vivo biocompatibility.
Sulfolane is a useful industrial solvent. The oral LD50 values were: rats, I-7 to 2s7 g./kg.; mice, I-9 to 2. 5 g./kg., all deaths taking place within 24 hours. Rats showed no effects after 3-8 g./kg. had been applied to the skin. The compound did not irritate or sensitize the skins of guinea-pigs or rabbits and, undiluted, was almost without action on the eyes of rabbits.
Dimethyl sulphoxide has good solvent properties for a wide range of chemicals, and a low toxicity to mammals. The acute oral LD50 for rats is about 20ml./kg. and for chickens about 12·5 ml./kg. Rats tolerate up to 10 daily doses of 10 ml./kg. weight. Dimethyl sulphoxide is therefore a useful solvent for chemical compounds under toxicological evaluation.
Spraying or swabbing with a mixture of polyethylene glycol 300/industrial methylated spirits (PEG-300/IMS) (2:1 by volume) has been shown to substantially reduce mortality, systemic effects, and skin burns resulting from skin contamination by phenol, cumene hydroperoxide, or phenol/acetone cleavage product. The skin-damaging potentials of sodium hydroxide and sulfuric acid have also been investigated. PEG-300/IMS(2:1 by volume) mixture was found, in rats, to be slightly less effective than water as means of decontamination. The PEG-300/IMS mixture has been shown not to cause eye irritation, and so should not present a hazard where this mixture is used as a decontaminant spray.
Summary Twelve mineral oils, originating from naphthenic and paraffinic stocks and variously refined, were evaluated for their potential to induce cutaneous neoplasia in female CF1 mice. The oils were applied to the shorn dorsal skin for up to 78 weeks, using several different treatment regimes.The sole acid/earth refined naphthenic spindle oil was a moderately potent cutaneous carcinogen. By comparison, the 11 oils, processed by other refining routes, were less carcinogenic or non-carcinogenic to murine skin. Two of the 11 oils were weak cutaneous carcinogens viz, a naphthenic spindle oil refined only by mild hydrotreatment and a paraffinic spindle oil refined by mild solvent extraction and 'Ferrofining'. All 9 remaining oils had been solvent-extracted as part of the secondary refining process; none induced malignant tumours, although solitary benign tumours of the treated site were recorded after exposure to 3 oils.The cutaneous carcinogenic potential of the test oils did not correlate well with their potential to induce epidermal hyperplasia at the treated site. Consequently, hyperplasia caused after short term exposure is of little value for distinguishing between carcinogenic and non-carcinogenic oils.
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