Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase.

The LD50 of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in the acute toxicity of DMN.     

Elimination and metabolism of dimethylnitrosamine (DMN) byXenopus laevis and other amphibians

Summary The elimination of (¹⁴C)-DMN after i.p. injection intoXenopus was measured, as was the metabolism in vitro of (¹⁴C)-DMN by liver fromXenopus and 9 other amphibian species. In view of its rapid elimination from the body and low rate of metabolism byXenopus liver in vitro, DMN is unlikely to be toxic or carcinogenic inXenopus.This work was supported by a grant from the Cancer Research Campaign. We are also grateful to Dr P. F. Swann, both for the supply of DMN and DEN and for many useful discussions.     

Elimination and metabolism of dimethylnitrosamine (DMN) by Xenopus laevis and other amphibians

The elimination of (14C)-DMN after i.p. injection into Xenopus was measured, as was the metabolism in vitro of (14C)-DMN by liver from Xenopus and 9 other amphibian species. In view of its rapid elimination from the body and low rate of metabolism by Xenopus liver in vitro, DMN is unlikely to be toxic or carcinogenic in Xenopus.     

Inhibition of rat hepatic dimethylnitrosamine demethylase by cyclic and acyclic nitrosamines and secondary amines

Summary Inhibition of hepatic dimethylnitrosamine (DMN) metabolism by a variety of cyclic and acyclic nitrosamines was demonstrated. Nitrosoproline, a noncarcinogenic nitrosamine, behaved differently from the carcinogenic nitrosamines as an inhibitor for DMN-demethylase. Secondary amines corresponding to the nitrosamines inhibited DMN-demethylase in a manner similar to the nitrosamines.Acknowledgments. This work was supported by Public Health Service Grant 5-PO1-ES00597, Training Grant 1-732-ES07020, and Research Career Development Award 1-KO4-ES00033 (to M.C.A.) from the National Institute of Environmental Health Sciences. We are also grateful for support from Hoffmann-LaRoche Inc., Nutley, NJ.     

Acute toxicity of folic acid in mice

Summary The toxicity of folic acid (PGA) was studied in different inbred strains of mice. LD₅₀ values of PGA by the i.p. route showed a unique toxicity pattern. In some strains, convulsions, ataxia and weakness were observed. Histopathological study in strains S/RVCri, BDF₁, DBA/2 and DBA/2fNCri showed acute renal tubular necrosis.Acknowledgment. The authors thank Ms N. Hasgekar for her technical assistance     

Acute toxicity of folic acid in mice

The toxicity of folic acid (PGA) was studied in different inbred strains of mice. LD50 values of PGA by the i.p. route showed a unique toxicity pattern. In some strains, convulsions, ataxia and weakness were observed. Histopathological study in strains S/RVCri, BDF1, DBA/2 and DBA/2fNCri showed acute renal tubular necrosis.     

Acute inhalation toxicity of ammonia in rabbits]

The aggressivity of ammonia at the pulmonary alveole level (intoxications in controlled ventilation) leads to an acute pulmonary oedema and cardio-vascular disfunctioning. Bradycardia is an early symptome (2,500 X 10(-6) but the real syndrome appears at 5,000 X 10(-6). Arterial pressure variations and blood gases modifications are significant, acidosis is systematic.     

A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors

The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect in unrelated to beta-adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP.     

A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors

Summary The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect is unrelated to -adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP.I thank Mrs Petra Lauck for help. This work was supported by the Deutsche Forschungsgemeinschaft.     

Variation in the toxicity of various silicas in relation to the duration of presence in the body]

The toxic effect of two forms of sand on the lung was investigated by tracheal injection in Rats. After a latent period with low toxicity, more and more extensive pulmonary lesions, comparable to typical silicotic lesions, appear progressively. On the basis of some observations, the hypothesis is put forward that the impurities present in the dust have a retardative effect.     

Inhibition of the morphogenesis of the otoliths in the chick embryo in the presence of carbonic anhydrase inhibitors

Riassunto Vengono studiati gli effetti sullo sviluppo del labirinto membranoso dell'embrione di pollo di alcuni inibitori della anidrasi carbonica (acetazolamide, dichlorofenamide, etossizolamide, neptazano). L'azione di tali sostanze si manifesta con una elettiva inibizione della morfogenesi degli otoconi.     

Metabolism of dimethylnitrosamine by amphibians and fish in vitro

Résumé On a examiné le métabolism de la (C¹⁴)-DMN par des coupes de foie de truite, de poisson rouge et de trois espèces d'amphibiens, ainsi que l'excretion du cancérogène après injection par voie intrapéritonéale chez le triton et le poisson rouge. La relation entre le métabolisme et l'activité toxique et/ou cancérogène est discutée.     

Acute toxicity and elimination of phenol injected into fish (Carassius auratus L.)

Riassunto Nel ciprino la DLM del fenolo è di 230 mg/kg i.m. Il fenolo, iniettato i.m. a dose di 200 mg/kg, viene eliminato in media per quasi il 90% nelle prime 4 ore come fenoli liberi. Sotto il profilo della tossicità, la mancata capacità a detossicare mediante coniugazione sembra nel pesce compensata dalla elevata capacità escretiva degli organi emuntori.     

Acute toxicity of copper and its probable effect on thyroid of the fry ofOphiocephalus punctatus (Bloch)

Summary LC₅₀ values for 24, 48, 72, 96 and 120 h were estimated at 1.507; 1.065; 0.785; 0.607; 0.559 mg/l copper respectively for the fry ofOphiocephalus punctatus. Copper induced hyperthyroidism resulting in exopthalmos, has been reported for the first time.