Chronic experiment

No treatment-related gross or histopathological lesions in the liver were observed in rats in the chronic experiment by NTP (1986), but dosed male mice had increased coagulative necrosis and hepatocytomegaly, along with increased incidences of hepatocellular adenomas and carcinomas (see Section 2.2.2.8 on carcinogenicity). Female mice, however, did not have treatment-related lesions in the liver. The highest dose (500 mg/kg/day) is indicated as a NOAEL for liver effects in rats, while the low dose (250 mg/kg/day) is indicated as a LOAEL for non-neoplastic liver lesions in... 

Gonadotoxicity of RVX was investigated in chronic experiments for different ways of introduction. Dermal exposure of male rats to RVX demonstrated that general toxic effects were the governing factor of gonadotoxicity. There were no gonadotoxic effects at the level of threshold... 

Goncharov, N.V., Mindukshev, I.V., Radilov, A.S., Kuznetsov, A.V., Dohrylko, LA. (2001). Effects of VX low doses on rat platelets in chronic experiment. In Medical Aspects of Radiation and Chemical Safety. Proceedings of the Russian Scientific Conference, Saint Petersburg, pp. 281-4. (In Russian)... 

These tests are recommended for use in chronic experiments and are described in detail [11-13]. 

NOEL (no observed ejfect level) This represents the highest concentration or dose that does not show any experimental evidence of an effect on test organisms. Technically, a NOEL could be applied also to a short-term acute test. Nevertheless, in toxicological praxis a NOEL should be derived from a relatively wide data set, including long-term chronic experiments. At the other end of the real toxicity threshold lies the LOEL (lowest oh served effect level). 

FIGURE 36.7 Tumors. Nos 1-4 lung tumors (1st chronic experiment). Lung tumors from the 2nd chronic experiment (No. 5 originated from bronchial epithelium, No. 6 adenocarcinoma from bronchial glandular epithelium, No, 7 from alveolar epithelium). Malignant lymphomas (Nos 8, 9) with lymphocytes infiltrated systemically. 

On the basis of the finding that venlafaxine in contrast to all other antidepressants caused down regulation of p-adrenergic receptors in acute as well as in chronic experiments when tested in the rat pineal model [100, 101] a rapid onset of antidepressant action in the clinic seemed plausible. For a review of its therapeutic potential see also reference [102]. 

Quantitative chemical information is somewhat easier to come by from an in vivo experiment. Mini- or microelectrodes should be calibrated with standard solutions of well-behaved electroactive species before and, if possible, after implantation and experimentation. o-Dianisidine (3,3 -dimethoxyben-zidine) in 0.1 M H2SO4 was found very satisfactory. After implantation (and, in the chronic experiments, recovery), data can be obtained using chronoam-perometry. Using the calibration data as a standard it is possible to monitor the concentration of all species that are oxidizable at the applied potential. 

The cups are small plastic cylinders that are used to investigate the release of ammo acids from cortical structures m acute and chronic experiments. For acute experiments, Clark and Collins (1976) used a Perspex cup, 4 mm id, that was placed on the surface of the visual cortex. The junction between the brain and cup was sealed with soft white paraffin The cup contained 50 jjlL Ringer solution and was exchanged every 10 mm see Fig. 4) The ion composition of the solution could be changed to study effects on the release The ammo acids in the "exchanged" solution were determined and the temperature in the cup and the electrocorti-cogram of the surface in the cup were monitored. A bipolar platinum electrode was inserted 0.5 mm below the surface of the cortex either within or outside the cup for electrical stimulation During these experiments the animal was anesthetized... 

E. Determining Thresholds of Harmful Action in Chronic Experiments.. 107... 

Groth, D. H., Vignati, L., Lowry, L., Mackay, G., and Stokinger, H. E., 1973, Mutual antagonistic and synergistic effects of inorganic selenium and mercury salts in chronic experiments, in Trace Substances in Environmental Health (D. D. Hemphill, ed.), pp. 187-189, University of Missouri Press, Columbia, Missouri. 

Chronic experiments using combined exposures to multiple carcinogenic metals, such as would occur most frequently in human exposures (Waalkes and Oberdorster 1990), have not been carried out with cadmium. However, cadmium can both enhance and antagonize the carcinogenic effects of several organic carcinogens (Harrison and Heath 1986 Kurokawa et al. 1985 Wade et al. 1987 Waalkes et al. 1991c). The incidence of diethyl-... 

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