Stabilisers toxic effects

Six healthy subjects stabilised on lithium carbonate 300 mg three times daily (mean serum levels 0.43 mmol/L) were given furosemide 40 mg daily for 14 days. Five experienced some minor adverse effects, probably attributable to the furosemide, without significant changes in serum-lithium levels, but one subject experienced such a marked increase in the toxic effects of lithium that she withdrew from the study after taking both drugs for only 5 days. Her serum-lithium levels were found to have risen from 0.44 to 0.71 mmol/L. ... 

An established and elinieally important interaetion. For maximal absorption give the iron at least 2 hours after the penicillamine. This should reduce their admixture in the gut. Do not withdraw iron suddenly from patients stabilised on penicillamine because the marked increase in absorption that follows may precipitate penicillamine toxicity. The toxic effects of penicillamine seem to be dependent on the size of the dose and possibly also related to the rate at which the dosage is increased. Only ferrous sulfate and fumarate have been studied but other iron compounds would be expected to interact similarly. 

For possible migrants in HDPE, there are traces of complex organometallic catalysts (which can be reduced to a minimum by repeated washing), traces of stabilisers [1-5] as well as solvents that are left in the system. However, animal tests showed that no toxic effects are involved in general [6, 7]. It is recommended that benzophenone-based UV absorbents and antioxidants are not used in HDPE designed for packaging foods that contain fat, especially corn oil [3-5]. 

Zinc is non-toxic in general, however, a surplus of it can be stored in the bones and spleen, and the most significant toxic effect of zinc is fume fever, that can result from acute inhalation of zinc oxide fumes. Zinc oxide is used in the rubber industry (it is a catalyst during manufacture and also used as a heat dispenser in the final product), as well as in pigments for plastics and in wallpaper. It also functions as a UV stabiliser for plastics and rubbers. In addition to these, it is possible to find mercury vapour indoors, emitted mainly from the biocides used in paints. 

Finally, most light stabilisers are chemically reactive and some have caused toxic effects in tests on animals, but they are normally used at very low concentrations. 

UV) stabiliser, an antistatic agent, mineral oil, and plasticisers. Although it may not be necessary to determine all of these, it is necessary to be aware of any interference that these substances might have on the determination of any particular component. Also, there is the question of additive breakdown either during polymer manufacture or upon contact with the food. Here there are two considerations possible interference effects of breakdown products on the determination of the additive and the necessity to identify the breakdown products, which themselves must be considered for their toxic effects. 

Compounds for use as antioxidants have to fulfil a number of requirements in addition to their effectiveness in stabilising the polymer. For example, they must have low toxicity and be inexpensive. They must also be fully compatible with the polymer of choice since otherwise they tend to migrate to the surface where they impart an unacceptable appearance. Any such migration also depletes the concentration in the bulk which leads to a loss of protection for the polymer. 

Considerable interest has been expressed in the industrial use of stabilised hypothatous acids (water reacted with chlorine, bromine or iodine). This innovation imitates the stabilisation of oxidised bromide that occurs in natural systems.51 These occur as mechanisms of control on the surface of some aquatic plants in the mammalian immune defences.52 Certain marine algae produce hypobromous acid using bromoperoidases53 which is not only an effective mechanism but exhibits good specific toxicity. 

Apart from routine quality control actions, additive analysis is often called upon in relation to testing additive effectiveness as well as in connection with food packaging and medical plastics, where the identities and levels of potentially toxic substances must be accurately known and controlled. Food contact plastics are regulated by maximum concentrations allowable in the plastic, which applies to residual monomers and processing aids as well as additives [64-66]. Analytical measurements provide not only a method of quality control but also a means of establishing the loss of stabilisers as a function of material processing and product ageing. 

Organo-tin compounds have been used as catalysts, stabilisers for plastics and biocides. Tributyltin (TBT) species are very effective biocides, and have been incorporated as active agents in antifouling compounds for marine applications. However, TBT has seriously affected other marine organisms such as oysters, crabs and fish even at parts per billion and lower concentrations in water. Consequendy, the determinations of low levels of TBT and dibutyl tin (DBT), its less toxic primary degradation product in water and in biological materials, are very important. 

Primarily used extensively for PVC-U applications in Europe and the Far East viz. pipe, fittings and profile, lead stabilisers have been very cost effective heat stabilisers. For similar reasons, plus good insulation resistance, lead stabilisers have also been used in PVC-P in wire and cable across the world. Their toxicity hazards have been well known and controlled, particularly in relation to worker exposure. 

The most common is augmentation is with the mood stabiliser lithium carbonate. Indeed, lithium may be effective as monotherapy for depression but is not preferred because of its adverse effect profile and need for plasma concentration monitoring. Its prescription in combination with antidepressants that have failed to produce remission is more usual and evidence suggests that up to 50% of patients who have not responded to standard antidepressants can respond after lithium augmentation. Addition of lithium requires careful titration of the plasma concentration up to the therapeutic range, with periodic checks thereafter and monitoring for toxicity (see p. 389). 

The actual chemical nature of the support material may be and often is of direct importance to its usefulness as a support material.15 Silicas can react with small nucleophiles such as F-, OH- and CN. Thus, silica-supported fluorides are inactive, both as nucleophilic fluorinating agents and as bases. Similarly, silicas are not effective support materials for cyanides due to the formation of strong Si-CN bonds. For different reasons, an acidic clay would not be a suitable support for cyanides, due to the possible formation of toxic HCN. Charcoal is the most effective support material for stabilising Cu(I), probably due to its aromatic character.16 For many chemisorbed supported reagent catalysts, silicas are preferred since they give relatively strong surface bonds. However, Si-O-C bonds are hydrolytically vunerable and direct Si-C bonds are preferred.17... 

Phenytoin has a stabilising effect on the myocardial cells so that the toxic threshold of digoxin at which arrhythmias occur is raised. However, the bradycardic effects of the digitalis glycoside are not opposed and the lethal dose is unaltered, so that the cardiac arrest reported would appear to be the result of excessive bradycardia. It seems possible that the fall in plasma digitoxin levels may be due to a phenytoin-induced increase in the metabolism of the digitoxin by the liver. ... 

Information seems to be limited to the reports cited. The incidence of this interaction is uncertain and its development unpredictable. It would be imprudent to give furosemide or bumetanide to patients stabilised on lithium unless the effects can be well monitored bwause some patients may develop serious toxicity. Patients on lithium should be aware of the symptoms of lithium toxicity (see Lithium , (p.l 111)) and told to report them immediately should they occur. Consider increased monitoring of lithium levels in patients newly started on this combination. 

It was observed in the last section that most antioxidants and stabilisers are relatively low molar mass organic compounds which can be easily extracted by solvents or volatilised from the surface of the polymer at elevated temperature. This is a disadvantage in two ways. Firstly, the additives may migrate into the human environment, causing toxicity in foodstuffs or, as in the case of prostheses, directly in the body. Secondly, because they are lost from the polymer, their effectiveness is reduced. 

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