Toxicity chemical degradation products with

Chemical Stability Chemical degradation of the drug includes reactions such as hydrolysis, dehydration, oxidation, photochemical degradation, or reaction with excipients. The constant presence of water and oxygen in our environment means that exposure to moisture or oxygen can affect the chemical stability of a compound. Chemical stability is very important, not only because a sufficient amount of the dmg is needed at the time of administration for therapeutic purposes, but also because chemical degradation products may adversely affect the properties of the formulated product and may even be toxic. 

Table 1. Principal chemical warfare agent degradation products with associated chronic toxicity guidelines 2... 

The excellent ability of nonionics to solubilize and disperse hydrophobic soils such as fats, mineral oils, etc, in water leads to extensive use of this e of emulsifier. Their often superior detergency with respect to solids surfaces is due to a combination of relatively low critical micellar concentration (CMC), allowing emulsification to take place at low emulsifier concentrations, and an ability to adsorb hydrophobically to interfaces and thus, by steric repulsion forces, to disperse hydrophobic liquid or colloid matter. An important group of nonionic emulsifiers is based on ethoxylated alkyl alcohols. Increasing demands for biodegradability and low aquatic toxicity of degradation products of industrial chemicals is expected to make fatty alcohols ethoxylates and nonionic emulsifiers based on natural raw materials an even more important group of chemicals in the future. 

For organic toxic chemicals and their degradation products the number of possibilities is very high. The environmental samples composition usually is very complicated. Unambiguous identification needs serial-pai allel strategy of analysis with many-stage crosschecking of data. 

Consideration of the potential toxicity of the agent, any thermal degradation products, or products generated on contact with chemicals present will dictate safety measures. 

Benchmark 4 Prefer - Safer Chemical. Only organic chemicals with low inherent toxicity to humans and wildlife, that do not bio accumulate, and rapidly and completely degrade to benign degradation products or metabolites reach Benchmark 4. These are chemicals that would meet the principles of green chemistry that relate to hazard. 

The duration of such toxicity tests varies. In the USA, the FDA usually recommends a period of up to 2 years, whereas in Europe the recommended duration is usually much shorter. Chronic toxicity studies of biopharmaceuticals can also be complicated by their likely stimulation of an immune response in the recipient animals. In the context of new chemical entities (NCEs, i.e. low molecular weight traditional chemicals), not only can the drug itself exhibit a toxic effect, but so potentially can drug breakdown products. As proteins are degraded to amino acids, any potentially toxicity associated with protein-based drugs is typically associated with the protein itself and not degradation products. 

The presence of surfactants and their biodegradation products in different environmental compartments can invoke a negative effect on the biota. The ecotoxicity of surfactants to aquatic life has been summarised in the scientific literature [1—5]. Nevertheless, some information is still lacking in relation to the aquatic toxicity of surfactants, especially knowledge regarding the toxicity of the degradation products, the effect of surfactants on marine species, the ecotoxicity of mixtures of chemical compounds with surfactants, the relationship between toxicity and chemical residue and the effect of surfactant presence in specific environmental compartments (water, particulate matter, pore-water, sediment). 

Not all agents can be readily metabolized. The toxic metals lead and mercury are elements that cannot be degraded but must still be removed from the body. Another important mechanism of detoxification is the attachment or binding of another compound to a toxic chemical to make it easier for the kidney to filter the compound out of the blood and excrete it in the urine. A primary purpose of the kidney is to screen the blood for waste products and concentrate them in the urine for excretion, as occurs, for example, with mercury. Caffeine is excreted in the urine at approximately the same concentration as the blood because the kidney cannot concentrate caffeine. Vitamins, however, are readily concentrated and excess quickly eliminated in the urine. 

Environmental toxicology is concerned with the movement of toxicants and their metabolites and degradation products in the environment and in food chains and with the effect of such contaminants on individuals and, especially, populations. Because of the large number of industrial chemicals and possibilities for exposure, as well as the mosaic of overlapping laws that govern such exposure, this area of applied toxicology is well developed. 

Once chemical agents are fully dispersed, they do not tend to persist in the environment because of their high chemical reactivity, particularly with water (hydrolysis). However, in extremely dry desert climates, they can persist for considerable periods of time (U.S. Army, 1988). The major environmental degradation products of nerve and mustard agents have recently been assessed and their persistence and toxicity evaluated. A potential hydrolysis product of VX (S-(2-diisopropylaminoethyl) methylphosphonothioic acid [EA-2192]) is a degradation product expected to display a high level of mammalian toxicity. Some mustard partial hydrolysis products are also toxic (Munro et al., 1999). 

For the purpose of implementing the CWC, toxic chemicals and precursors, which have been identified for the application of verification measures, are listed in Schedules contained in the Annex on Chemicals (for the Schedules, see Chapter 2). Schedule 1 includes chemicals developed, produced, stockpiled, or used as a chemical weapon as defined above, and chemicals structurally close to them. Schedule 2 lists three toxic chemicals not included in Schedule 1 and the degradation products and precursors of these toxic chemicals as well as of those of Schedule 1. Schedule 3 lists four toxic chemicals and precursors not listed in the other Schedules. The Schedules contain mainly organic chemicals with different chemical and physical properties, being neutral chemicals, acids, bases, volatiles, and nonvolatiles, where phosphorus, fluorine, sulfur, chlorine, nitrogen, and oxygen occur frequently. Riot control agents are not included in the Schedules. 

---