Animal experiments

The odor threshold for detection of ethyleneimine is 2 ppm. The maximum permissible concentration of ethyleneimine in the air at the place of work is 0.5 ppm (as specified in statutory regulations in the United States (374) and in Germany (375)). Animal experiments have shown ethyleneimine to be both carcinogenic (376) and mutagenic (377) (Table 2). 

Selenium. Selenium, thought to be widely distributed throughout body tissues, is present mostly as selenocysteine in selenoproteins or as selenomethionine (113,114). Animal experiments suggest that greater concentrations are in the kidney, Hver, and pancreas and lesser amounts are in the lungs, heart, spleen, skin, brain, and carcass (115). 

Toluenediamine is classed as toxic. The oral LD q for animals is between 270—350 mg /kg body weight (45). TDA is readily absorbed through the skin and this is the major route of human exposure. Several studies have shown the 2,4 isomer of TDA to be carcinogenic for rats and mice, but tests on the 2,5 and 2,6 isomers were not positive. AH three of the isomers have been shown to be mutagenic (45). Results of limited studies on the reproductive ha2ards for male workers are equivocal, but animal experiments have shown TDA to cause adverse reproductive effects (45). 

Biosynthesis of Protein. The dynamic equilibrium of body protein was confirmed by animal experiments using A/-labeled amino acids in 1939 (104). The human body is maintained by a continuous equilibrium between the biosynthesis of proteins and their degradative metabolism where the nitrogen lost as urea (about 85% of total excreted nitrogen) and other nitrogen compounds is about 12 g/d under ordinary conditions. The details of protein biosynthesis in living cells have been described (2,6) (see also Proteins). 

Fluconazole. This substance (19) is a water-soluble bis-triazole tertiary alcohol (33). Fluconazole [86586-75-4] h.3.s a broad spectmm, but has httie activity in vitro. However, animal experiments reveal a broad spectmm and a potent effect. 

The TLVs, as recommended and published by the ACGIH, refer to concentrations of airborne contaminants or levels of physical agents, and represent the conditions to which it is believed nearly all workers may be repeatedly exposed day after day without adverse effects. TLVs are based on the results of animal experiments, limited human experiments, some industrial experience and, when possible, a combination of all three. 

Hazard identification through animal experiments, epidemiological studies, or structure activity analyses... 

Small versions of downdraft tables (less than approximately 0.5 m-) are used when small-sized chemical work is to be done on rabies instead of in laboratory-fume hoods (see Fig. 10.37). This includes work with low-momentum source (no initial velocity and near room temperature) such as laboratory animal experiments. 

Not all contaminants or chemicals are created equal in their capacity to cause adi ersc effects. Thus, cleanup standards or action levels are based in part on the compounds toxicological properties. Toxicity data are derived largely from animal experiments in which llie aninuils (primarily mice mid rats) are exposed to increasingly liighcr concentrations or doses. Responses or effects can vary widely from no obscn ablc effect to temporary and reversible effects, to permanent injury to organs, to chronic functional impairment to ultimately, death. 

Because risk at low exposure levels is difficult to tneasure directly either by animal experiments or by epidemiologic studies, the development of a slope factor generally entails applying a model to the available data set and... 

Condensation of the lynestrol intermediate (47) with ethyl-magnesium bromide affords the oral androgen ethylestrenol (72) Animal experiments on the various drugs above have all shown increased anabolic effects relative to androgenicity. 

In the aitways, inhibition of PDE4 is much more antiinflammatory than bronchodilatory. Although effective in animal experiments, the neuronal and gastric side effects of PDE4-inhibitors have so far impeded their use in humans. Two new orally active PDE4-inhibitors (roflumilast, cilomilast) have shown some effectiveness in advanced clinical trials, but have not yet been approved. 

Evidence for this human health linkage has been suggested from (a) epidemiologic studies of exposed human populations, (b) human volunteer studies, and (c) animal experiments 14). Air pollution levels measured in southwestern Ontario, for instance, have been compared with hospital... 

Public concern about PBDE levels in the environment was heightened when it was shown that a sharp increase in the concentration of certain PBDEs had occurred in human breast milk over only a 10-year period (Meironyte et al. 1999 Noren and Meironyte 2000), and the levels of exposure in some infants and toddlers were similar to those shown to cause developmental neurotoxicity in animal experiments (Costa and Giordano 2007). As a result of these concerns, the majority of commercial PBDE mixtures have been banned from manufacture, sale, and use within the European Union. 

There is ample evidence from both animal experiments and tissue cultures studies to show that brassica vegetables and their constituents selectively induce Phase II enzymes. Evidence for the induction of Phase II enzymes by... 

Cardiovascular disease (CVD) is characterized by the involvement of the heart and allied vascular system. High cholesterol, associated lipid abnormahties and high blood pressure are recognized as the major risk factors of CVD. There have been several animal experiments and clinical studies using rice bran and rice bran oil, which have demonstrated a hypocholesterolemic effect (Raghuram et al., 1989 Rukmini and Raghuram, 1991 Sugano and Tsuji, 1997). The mechanisms involved are briefly summarized. 

Since the results of our experiments with isolated rat liver fractions supported a reaction sequence Initiated by microsomal oxidation of the nitrosamine leading to formation of a carbonium ion, the results of the animal experiment suggested that in the intact hepatocyte, one of the earlier electrophilic intermediates (II, III or V, Figure 1) is intercepted by nucleophilic sites in DNA (exemplified here by the N7 position of guanine) before a carbocation is formed. 

The degree of confidence in the final estimation of risk depends on variability, uncertainty, and assumptions identified in all previous steps. The nature of the information available for risk characterization and the associated uncertainties can vary widely, and no single approach is suitable for all hazard and exposure scenarios. In cases in which risk characterization is concluded before human exposure occurs, for example, with food additives that require prior approval, both hazard identification and hazard characterization are largely dependent on animal experiments. And exposure is a theoretical estimate based on predicted uses or residue levels. In contrast, in cases of prior human exposure, hazard identification and hazard characterization may be based on studies in humans and exposure assessment can be based on real-life, actual intake measurements. The influence of estimates and assumptions can be evaluated by using sensitivity and uncertainty analyses. - Risk assessment procedures differ in a range of possible options from relatively unso-... 

Acknowledgements We thank Dr. Angelika Lorenz and Dr. Jurgen Proll for conducting the animal experiments. This work was financially supported by the Federal Ministry for Education, Science, Research and Technology. 

The parameters below come either from animal experiments or epidemiological... 

Animal experiments into the effect of ingestion of chryso-tile asbestos demonstrated an accumulation of cellular debris within the lumen of the ileum and colon consistent with cytotoxic changes of the mucosal lining cells (Jacobs etal., 1978). The question as to whether asbestos causes tumours in the gastrointestinal tract in humans is a topic of concern, however, the evidence remains equivocal (Levine, 1985). 

Rules and filters do exceptions exist Off course they do. Common sense is required. There is a natural priority order in drug discovery decision making. Clinical information trumps all. Next in importance is high quality experimental evidence, e.g., in vivo animal experiments. Rules and filters come into play when clinical and experimental data is lacking. 

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