Toxicity studies activity

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

Argatroban [74863-84-6] ((2R,4R)-4-methyl-l-[A/ -)(3 methyl l,2,3,4-tetrahydto-8-quiaoIiaesulfonyl)-L-atgiayl]-2-piperidiaecatboxyhc acid monohydrate) is a potent inhibitor of thrombin formation and activity (49). This agent has been studied in vitro and ia a few animal models. Its toxicity and activity ia humans ate unknown. 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

Hoechst. 1985 a. Endosulfan-active ingredient technical (Code HOE 02671 OIID970003) 13-week toxicity study in rats followed by a 4-week withdrawal period, conducted at Huntingdon Research Center, England. Hoechst Aktiengesellschaft, Frankfurt, West Germany. Unpublished study, [unpublished study]... 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

In addition to the well-characterized role of iron in catalysing redox interactions, other metallic contaminants, for example, nickel, may also contribute. In vivo toxicity studies have demonstrated the capacity of nickel particulate compounds to induce tumours following intraperitoneal injection (Pott etal., 1987). Such activity is proportional to their phagocytic uptake, and to the associated respiratory burst and generation of PMN-derived reactive oxygen metabolites (ROMs), a proposed pathogenic mechanism (Evans et al., 1992a). 

Single-dose oral toxicity studies in rats, mice, and cattle indicate that signs of diisopropyl methylphosphonate intoxication include decreased activity, ataxia, tympanitis, and prostration within 1-4 hours after dosing (Hart 1976 Palmer et al. 1979). Mink that received 1,852 mg/kg/day diisopropyl methylphosphonate in their feed displayed aggressive behavior. However, it was concluded that this behavior was probably due to hunger resulting from the unpalatability of the feed (Aulerich et al. 1979). 

Ameller T, Marsaud V, Legrand P, Gref R, Renoir JM (2004) Pure antiestrogen RU 58668-loaded nanospheres morphology, cell activity and toxicity studies. Eur J Pharm Sci 21 361-370... 

But the most-used toxicity tests are based on bioluminescence inhibition, the responses of which are sometimes difficult to interpret particularly for waste-water quality monitoring. A comparison between a bioluminescence test kit (Microtox) and a respirometry approach for the toxicity study of seven organic and five inorganic toxic compounds was performed [54]. The bioluminescent response proved to have a higher sensitivity to toxicants but was less representative of the effects on activated sludge compared to respirometry, due to the nature of the microorganisms involved in each procedure. 

Safety Pharmacology. It is important to investigate the potential for unwanted pharmacological activity in appropriate animal models and to incorporate monitoring for these activities in the toxicity studies. 

Dose selection is one of the most important activities in the design of a toxicology study. It is especially critical in carcinogenicity studies because of their long duration. Whereas faulty dose selection in an acute or subchronic toxicity study can easily be corrected by repeating the study, this situation is much less desirable in... 

Traditionally, the duration of a toxicity study depends on the intended clinical use and disease duration. The potential immunogenicity of the human protein is a significant issue since antibody binding can partially or completely inhibit the biological activity of that protein, affect its catabolism or alter its distribution and clearance. Any multiple-dose study therefore should include evaluation of the impact of antibody formation, including their neutralizing capacity. However, antibody formation in itself should not be a reason for termination of a toxicity study, particularly if the antibodies are not neutralizing or do not alter the pharmacodynamics of the protein. 

Mihail F. 1978. S 276 (Disyston active ingredient) acute toxicity studies. Report no. 7602a. AG Bayer, Institute fur Toxicologie, West Germany. 

Thomas DA, Morgan KT. 1988. Olfactory toxicity Studies of methyl bromide. CUT Activities 8 3-7. 

Hermens, J., Canton, H., Janssen, P., and de Jong, R. Quantitative structure-activity relationships and toxicity studies of mixtures of chemicals with an anaesthetic potency acute lethal and sublethal toxicity to Daphnia magna, Aquat. Toxicol, 5(2) 143-154, 1984. 

Konemann, H. Quantitative structure-activity relationships in fish toxicity studies. Part 1 relationship for 50 industrial pollutants, Toxicology, 19(3) 209-221, 1981. 

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