Toxicity profiles

Chloroacetic Acid—Toxicity Profile," The British Industrial Biological Research Association (BIBRA), Surrey, England, 1988. 

Immunosuppression induced by sirolimus (36) appears to be mediated by a mechanism distincdy different from that of either cyclosporin or FK-506. Sirolimus markedly suppresses IL-2 or IL-4-driven T-ceU proliferation. The preclinical studies suggest that sirolimus is a potent immunosuppressive agent in transplantation and autoimmune disease models. The clinical potential of this agent depends on its toxicity profile (80). 

Pigments and Extenders. Pigments are selected for use in house paints based on thek appearance and performance quaUties. Appearance includes color and opacifying abiUty. Performance quaUties include ultraviolet light resistance, fade resistance, exterior weatherabiUty, chemical resistance, as well as particle size and shape. Toxicity profiles and safety and health related properties are also important criteria in pigment selection. 

Solvents. Solvents in house paints serve several essential purposes. They keep the binder dispersed or dissolved and the pigments dispersed in an easy-to-use state. Solvents allow the paint to be appHed in the correct thickness and uniformity, and evaporate from the paint film after the paint is apphed. Solvent choice is limited mainly to a solvent that is compatible with the binder system and that has the desked evaporation rate and toxicity profile. The volatility or evaporation rate of a solvent determines to a large extent the open-time and dry-time properties of a paint (6). 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

Toxicology studies must be performed in at least two animal species. If the toxicity profile of the compound is acceptable, then it joins the hit or lead list of compounds to proceed. The metabolism of the compound must be understood and pharmacokinetic studies must be performed in small and large animals. Efficacy studies must be performed in relevant animal models, especially in chimpanzees when more than one candidate is identified and a choice has to be made before proceeding to studies in humans. The ultimate preclinical steps include various studies testing drug combinations in vitro and in vivo, selection of resistant viruses, viral fitness, pyrophosphorolysis, and others. 

Vettorazzi G. 1979. International regulatory aspects for pesticide chemicals Volume I. Toxicity profiles. Boca Raton, PL CRC Press, Inc. 

There is a vast range of aqueous organic pollutants with a wide toxicity profile. Some, e.g. polychlorinated biphenyls, certain herbicides, fungicides and pesticides, and organo-mercury compounds, are persistent and may bioaccumulate in the food chain. Trace contaminants such as sodium chloride, iron and phenols (especially if chlorinated) may also impart a taste to water. Typical consent levels for industrial discharges are provided in Table 13.10. 

Capedtabine is the prodrug of 5-FU and comes as oral tablets that are administered with food twice a day. Capedtabine has shown to be active in tumors of the colon, rectum, and breast. The toxicity profile of capecitabine is similar to that of 5-FU and includes diarrhea, mucositis, palmar-plantar erythrodysesthesia,... 

Another concern is the coinfusion of intravenous medications with PN admixtures. Many intravenous medications have limited compatibility with 3-in-l formulations but may be coinfused with a 2-and-l formulation.23,24 Some medications can be coinfused at the Y-site, few medications can be mixed directly into the PN solution or coinfused with intravenous lipid emulsion, and some cannot be mixed or coinfused with the PN admixture.23,24 Always consult compatibility data before adding a medication to a PN admixture or coinfusing with PN. Medications that are compatible should be added to PN only if it is reasonable and safe (i.e., based on toxicity profile, pharma-cokinetic/pharmacodynamic considerations). 

IPBC, (see Figure 8) is used extensively by the wood preservation industry. It has an excellent toxicity profile and is extremely efficacious against fungi. 

Harikumar, K. B., C. V. Nimita et al. (2008). Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta). Int. J. Toxicol. 27(1) 1-9. 

Nitroheteroarenes continue to attract research activity. A series of 5-nitro-2-furyl derivatives were evaluated for in vivo efficacy against T cruzi [64] and an improved toxicity profile. Compound 65 showed a good efficacy profile in vivo and better acute toxicity profile when compared to nifurti-mox. A series of 5-nitroindazoles, represented by 66 (IC50 = 7.4 iM), were reported as having activity similar to nifurtimox (IC50 = 3.4 iM) in a growth inhibition assay [65]. 

The development of lithium-specific electrodes has assisted greatly in monitoring patient compliance. The toxicity profile of lithium carbonate is now well established and the drug is safely administered and well tolerated. It is of limited use in other psychiatric disorders such as pathological aggression, although additional benefit may also include a reduction in actual or attempted suicide. 

Pt(TV) Prodrugs. Platinum(IV) complexes have been widely studied as potential prodrugs that avoid the limitations of the cisplatin class of anticancer drugs. Indeed, the Pt(IV) compound satraplatin [Pt(cha)Cl2(OAc)2(NH3)] (cha, cyclohexylamine) is currently in clinical trials for treatment of hormone-refractory prostate cancer (Fig. 1) (22). Satraplatin is the first orally bioavailable platinum derivative under active clinical investigation and is particularly attractive because of the convenience of administration, milder toxicity profile, and lack of cross-resistance with cisplatin. These results are promising and support the idea that platinum(IV) complexes offer the opportunity to overcome some of the problems associated with cisplatin and its analogs. 

Even the toxicity profile is more advantageous, as seen in table 4. 

Whilst the pigment has a favourable toxicity profile and a long history of application in sensitive applications such as cosmetics and in food-contact applications, in order to meet the requirements of discerning customers practice sustainable procurement and look for products with a beneficial life cycle analysis. This paper, therefore, outlines the results of a study which shows how a commitment to sustainable manufacture is an essential addition to the favourable toxicity profile. Areas for improvement are recognised and options for renewable energy resources are discussed. 

It is accepted that many widely used latex vulcanisation accelerators - dithiocaibamates, thiurams and thiazoles - are capable of producing Type IV allergic response in certain individuals within the population and may also possess increasingly unacceptable eco-toxic and acute toxicity profiles. Thiurams and dithiocaibamates (derived from secondary amines) can also produce potentially harmful N-nitrosamines. Four safer accelerators developed and commercialised by Robinson Brothers are described. They are designed to reduce or eliminate the impact of the above problems using sustainable technology. At the same time these accelerators produce equivalent technological performances to those conventionally used. 10 refs. 

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