Anthony M. Ambrose

The reversible nephrotoxic effects of biphenyl

Abstract Rats ingesting diets containing 0.5% biphenyl developed nephrotoxic effects including focal tubular dilation in approximately 60 days. Rats returned to control diet for 60 days after ingesting a dietary level of 0.5% biphenyl for 165 days showed a regression of kidney lesions with scar formation. A more sensitive criterion of the renal effects of biphenyl was polyuria, which is probably a defense mechanism response to the irritant action caused by the insoluble biphenyl metabolites passing through the kidney. No evidence of either polyuria or histopathologic damage was observed from the ingestion of 0.1% biphenyl in the diet for 120 days.

Pharmacologic and toxicologic studies of N,N-diethyltoluamide: N,N-Diethyl-o-toluamide and N,N-Diethyl-p-toluamide☆

Toxicologic data are presented on two isomers of N,N-diethyltoluamide, namely, N,N-diethyl-o-toluamide (o-DET) and N,N-diethyl-p-toluamide (p-DET), which appear as impurities in N,N-diethyl-m-toluamide (m-DET), a new insect repellent. The acute oral LD50 for rats, both sexes, is of the order of 1.21 ± 0.042 g/kg for o-DET and 2.3 ± 0.19 g/kg for p-DET. Repeated daily gastric intubation of 50% of the estimated LD50 values to rats for 19 days showed no evidence of adverse effects, either grossly or histologically. Feeding diets containing 0.0, 0.01, 0.05, 0.1, 0.5, and 1.0% (equivalent to 0, 100, 500, 1000, 5000, and 10,000 ppm) of o-DET or p-DET for 30 weeks to rats revealed no serious deleterious effects other than a slight depression in growth for female rats on the two highest concentrations of o-DET in the diet; hypertrophy of the livers of both male and female rats on 0.5 and 1.0% o-DET or p-DET; and hypertrophy of the kidneys of male rats on 1.0% and female rats on 0.5 and 1.0% o-DET. Minimal morphologic changes observed in the kidneys of rats on the various dietary levels of o-DET or p-DET are considered to be insignificant and unrelated to the compounds fed. Other organs were unaffected. Repeated cutaneous application of o-DET or p-DET in doses of 200 mg/kg/day for 65 days to rabbits and 260 mg/day to rats for 20 days produced only minor, fleeting and incipient skin reactions and only minor or insignificant microscopic changes in the kidneys only. On mucous membranes of the eye, no irritation, chemosis or conjunctivitis was observed.

Acute and Subacute Toxicity of Pure Gitrinin

Conclusions The lower toxicity values reported by Robinson, as compared with those reported by Timonin and Routt and those reported here, may be due to a low rate of absorption fo citrinin from a suspension in gum solution. Citrinin in solution is rapidly absorbed, regardless of the mode of administration, as shown by the toxicity data. The production of tissue changes and the fact that citrinin may result in delayed deaths, up to fourteen days, would make a statement regardless an LD50 dose misleading.

Some Comparative Observations on l-Nicotine and Myosmine

Summary 1. The acute toxicity of myosmine was about one-tenth that of l-nicotine after oral administration. Intraperitoneally myosmine was about one-sixth as toxic as l-nicotine. 2. On isolated intestinal strips of guinea pigs, contraction by myosmine required about 200 times the concentration necessary in the case of l-nicotine. 3. Sulfa-thiazole inhibited the action of both myosmine and l-nicotine on isolated intestinal strips.

Comparative Studies on Toxicity of a New Streptomycin and Streptomycin Sulfate.

Investigators at the Northern Regional Research Laboratory of the U. S. Department of Agriculture have recently reported the isolation in pure state of a new antibiotic, hydroxystreptomycin. It is produced by an organism, isolated from Japanese soil, which they believe to be different from other streptomycin-producing strains. The new species has been designated as Streptomyces griseocarneus n. sp. On the basis of degradation experiments, Benedict et al.( 1 ) have assumed that the new antibiotic differs from streptomycin only in having a hydroxy group in place of one of the hydrogens of the streptose methyl group. Accordingly, they have assigned the name “hydroxystreptomycin” to the new member of the streptomycin series. One mg analytically pure hydroxystreptomycin trihydrochloride, when assayed against Bacillus subtilis, NRRL B-765 (ATCC 6633), was found to be equivalent to 784 jug of streptomycin base. The hydroxystreptomycin trihydrochloride used in these studies was prepared in the Northern Regional Research Laboratory and assayed 596 μg/mg (76% pure). The streptomycin sulfate assayed equivalent to 621 μg of pure free base per mg and was 78% pure.† In the present studies we have compared the acute toxicity of hydroxystreptomycin trihydrochloride against the toxicity of streptomycin sulfate in white mice by subcutaneous administration. Both samples of streptomycin were dissolved in glass distilled water just before use, and the pH of each solution was measured with a glass electrode. The pH of a 10% solution of hydroxystreptomycin trihydrochloride was 7.1; that of a 10% solution of streptomycin sulfate was 4.8, which was adjusted to 6.2 with solid sodium bicarbonate. At least 10 mice (sexes equally divided) were used at each dosage level in determining the toxicity of the 2 streptomycins. For hydroxystreptomycin trihydrochloride, 46 mice were used and for streptomycin sulfate, 60 mice were used. The approximate LD50, as determined by Trevans method, was found to be as follows: for hydroxystreptomycin trihydrochloride, 865 mg/kg; and for streptomycin sulfate, 970 mg/kg.