Chronic dermal studies of petroleum streams in mice.

During petroleum refining, a large number of products are generated which have varying chemical and physical properties. These are known in the industry as petroleum streams. In order to characterize their carcinogenic activity, a number of these commercially produced streams were administered to C3H/HeJ mice in chronic dermal bioassays. The bioassays were conducted using one of two study designs: the first set of test materials was applied for a lifetime and the second set for 24 months. In the lifetime study, the last mice in the test groups survived for periods of 31 to 32 months. Middle distillates, boiling in the range 115-390 degrees C, were found to decrease the lifespan of exposed mice compared to controls or streams of higher and lower boiling ranges. These middle distillate streams included straight run kerosine, hydrodesulfurized middle distillate, straight run middle distillate, light catalytic cracked distillate, and 90/10% and 70/30% mixtures of the last two. The middle distillate streams also proved to be active as carcinogens, with tumor incidence ranging from 16 to 67%. Light alkylate naphtha, heavy catalytic reformed naphtha, vacuum residuum, and unleaded gasoline did not demonstrate significant carcinogenic potency. Heavy thermal cracked naphtha, heavy catalytic cracked naphtha, and hydrotreated light naphthenic distillate were dermal carcinogens of low potency in this study. Administration of light catalytic cracked naphtha led to a low incidence of very late developing tumors with a mean latency of 118 weeks. Application of the 0.1% solution of catalytic cracked clarified oil in toluene did not result in a significant incidence of tumors, but the 10% solution caused almost 100% mortality and 100% tumor incidence in 12 months. There was no correlation between carcinogenic potency and the indices of irritation, alopecia, erythema, and scabbing. Only two of the streams tested, hydrotreated light naphthenic distillate and 10% catalytic cracked clarified oil, contain polynuclear aromatic hydrocarbons (PNAs) and may be presumed to be complete carcinogens. The middle distillates and heavy naphthas are nonmutagenic and essentially free of PNAs. Their activity may result from promotion of already-initiated skin sites. Where comparisons could be made, reducing the exposure period from a lifetime (29-32 months) to 24 months did not change the evaluations of stream carcinogenicity except in the case of light catalytic cracked naphtha where six of the seven mice that developed tumors did so after 24 months.

Effect of cefamandole nafate on the toxicity of tobramycin.

Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase the acute toxicity (lethality) of tobramycin in rats or mice. In a subacute experiment in rats, dose-related tobramycin nephrotoxicity, as evidenced by blood urea nitrogen changes, increased kidney weights, and histologically determined tubular nephrosis and necrosis, was observed. Concomitant treatment with cefamandole nafate, 500 mg/kg, did not increase tobramycin nephrotoxicity, but protected against the aminoglycoside-induced renal injury. Determination of tissue radioactivity after administration of [(14)C]tobramycin indicated that cefamandole nafate treatment resulted in uniformly lower tobramycin tissue concentrations compared with the control, suggesting that the protective effect was produced by enhanced excretion of tobramycin after cefamandole nafate treatment.