Persistence of toxicity

As seen further on in this chapter, individual PEEP index values express a condensed portrait of an effluent s hazard potential which takes into account several important ecotoxicological notions (toxic intensity and scope in terms of biotic levels impacted, bioavailability, persistence of toxicity and effluent flow). Unlike wastewater investigations limited to chemical characterization, this bioassay-based scale reflects the integrated responses of several representative toxicity tests to all interaction phenomena (antagonistic, additive and/or synergistic effects) that can be present in effluent samples. 

Animals that comprise the satellite group for follow-up studies should be kept under observation for 14 days without treatment. This procedure detects persistence of toxic effects (if any), as well as manner of recovery. A careful clinical examination should be made every day. Action should be taken to minimize the loss of experimental animals, (e.g., identifying animals that are moribund, doing necropsy, refrigeration of animals that are found dead, sacrificing weak or moribund animals). 

The observation period for the subchronic oral toxicity should be at least 90 days. Animals in a satellite group scheduled for follow-up observations should be kept for a further period of 28 days without treatment to detect recovery from, or persistence of, toxic effects. Careful clinical examination should be made at least once each day. Additional observations should be made and appropriate actions taken to minimize loss of animals these actions include necropsy or refrigeration of those found dead, or isolation, or sacrifice of weak or moribund animals. The animals are dosed with the test chemical ideally 7 days per week for 90 days. However, based primarily on practical considerations, dosing by gavage or capsules 5 days per week is acceptable. 

Solubility Issues Another reason for the persistence of toxicity is its insolubility. It may be possible that it is partly due to the hydrophobic nature of the CNTs and also their propensity to aggregate and interact with the cell membranes. There are chances that these conditions may be mitigated by surface modifications of CNTs. According to one study, if the CNTs are modified to increase their solubility and decrease their surface hydrophobicity, eventually it results in decrease of the CNTs cytotoxicity [35]. Therefore, in order to attain a successful application in medicine, it becomes a prerequisite to purify and chemically modify the CNTs in order to increase their solubility and decrease the level of toxicity. Through the mechanism of chemical functionalization, water soluble CNTs can be modified. This helps to bind them to selective therapeutics or biologically relevant molecules [36]. 

Schimmel SC, Gamas RE, Patrick JM, et al. 1983. Acute toxicity, bioconcentration and persistence of AC 222,705, benthiocarb, chlorpyrifos, fenvalerate, methyl parathion and permethrin in the estuarine environment. J Agric Food Chem 31 104-113. 

In discussing the enviromnental fate of technical DDT, the main issue is the persistence of p,p -DDT and its stable metabolites, although it should be bom in mind that certain other compounds— notably, o,p -DDT and p,p -DDD—also occur in the technical material and are released into the environment when it is used. The o,p isomer of DDT is neither very persistent nor very acutely toxic it does, however, have estrogenic properties (see Section 5.2.4). A factor favoring more rapid metabolism of the o,p isomer compared to the p,p isomer is the presence, on one of the benzene rings, of an unchlorinated para position, which is available for oxidative attack. p,p -DDD, the other major impurity of technical DDT, is the main component of technical DDD, which has been used as an insecticide in its own right (rhothane). p,p -DDD is also generated in the environment as a metabolite of p,p -DDT. In practice, the most abundant and widespread residues of DDT found in the environment have been p,p -DDE, p,p -DDT, and p,p -DDD. 

Apart from the oxidations just mentioned, cyclodienes are rather stable chemically. It should, however, be noted that dieldrin can undergo photochemical rearrangement under the influence of sunlight to the persistent and toxic molecule photo dieldrin, which occurs as a residue following the application of this insecticide in the field. 

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

This process shonld be considered in the light of the preceding comments on association. Many experiments on the recoverability, persistence, and toxicity of xenobiotics have used spiked samples that do not take into acconnt the cardinal issne of alterations in the contaminant that have taken place after deposition. This is termed aging, and shonld be evalnated critically in determining persistence. Some examples are given below as illnstration for both terrestrial and aquatic systems ... 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

With respect to sampling, sufficient numbers of environmental samples should be obtained to permit reliable statistical and biologic Interpretation of results. At the same time, the samples collected should be from environmental locations where human exposure Is most likely to occur (or did occur. If questions of past exposures require assessment). They should also be targeted for those environmental media which can be expected to have the greatest potential for human exposure and absorption. Finally, the samples must be obtained and preserved so that the chemicals which pose the greatest threat for human health In terms of toxicity and tissue persistence can be accurately measured. 

The Danish List of Undesirable Substances is a list of chemicals of concern that the government believes should be avoided to the extent feasible in commerce. Using a systematic analysis, substances are selected automatically if they meet some clear and defined criteria, for example, problematic classifications, because they are imder suspicion for being PBT/vPvB (Persistent, Bioaccumulative, Toxic/very Persistent, very Bio accumulative) or endocrine-disrupting. 

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