Formaldehyde-releasing compound

Richardson, C.R., Styles, J.A. Burlinson, B. (1983) Evaluation of some formaldehyde-release compounds and other biocides in the mouse mieronueleus test. Mutat. Res., 124, 241-246... 

Although imidurea releases formaldehyde, it does not appear to be associated with cross-sensitization with formaldehyde or other formaldehyde-releasing compounds. 

Cosmetic preparations that contain formaldehyde donor compounds release formaldehyde in the presence of water. Very often, these are water-based preparations, such as shampoos. The presence of released formaldehyde is not required for the antimicrobial action of the compound and is therefore regarded as an nuisance however, this depends on the chemical formula as a whole. In the end, increasing use of formaldehyde-releasing compounds may lead to an increase in the incidence of contact allergy (Kranke et al. 1996). Formaldehyde-releasing agents include ... 

The resistance of certain Pseudomonas putida strains to formaldehyde and formaldehyde-releasing compounds is a case of intrinsic resistance attributable to the presence of the constitutive enzyme formaldehyde dismutase in these microbes (Adroer et al., 1990). The stoichiometric dismutation of formaldehyde to methanol and formic acid, known to chemists as Cannizaro s reaction, occurs under physiological conditions in microbe cells in which formaldehyde dismutase is present. Furthermore, if formaldehyde is supplied, this promotes in the cells the formation of formaldehyde dehydrogenase, an enzyme that catalyses the conversion of formaldehyde to formic acid (Kato et al., 1984). 

Benzyl alcohol is listed in the EC positive list of preservatives for cosmetic products (maximum concentration for application 10 000 mg/litre). The activity of benzyl alcohol is not very much affected by the pH and the composition of the medium to be protected. As an auxiliary solvent with antimicrobial efficacy benzyl alcohol is used in preservative compositions for industrial fluids (Paulus et al., 1970 z). A well-known preservative for cosmetics and industrial fluids is benzyl alcohol mono(poly)hemiformal (Paulus, 1976) which is a formaldehyde releasing compound and therefore listed in Section 3.1.1. 

Formaldehyde as such is often too volatile and too reactive to be used as a micro-bicide for the protection of materials or in disinfectants. It additionally produces unwelcome side-effects, and has an insufficient balanced range of activity. One therefore has looked for formaldehyde releasing compounds which do not exhibit the disadvantageous formaldehyde effects but maintain or even improve the antimicrobial action of formaldehyde. 

Mould producing fungi are more tolerant of trimethylol nitromethane than bacteria. However, trimethylol nitromethane and other methylolnitro-hydrocarbons cannot be ranked among the very effective formaldehyde releasing compounds, although in alkaline media there is a noticeable increase of the tendency, especially of trimethylol nitromethane, to release formaldehyde accompanied by a corresponding increase in efficacy. A report of Clark et al (1974) surveys the synthesis and antimicrobial activity of aliphatic nitro compounds. 

Trimethylol nitromethane as a preservative for industrial fluids in the meantime has been widely substituted by more effective formaldehyde releasing compounds. However, its good skin compatibility and the fact that there is at no... 

Products obtained by reaction of formaldehyde and amines are always characterized by, among other properties, antimicrobial effectiveness. Here, too, the introduction of the methylol group is the first reaction step it may be followed by water being split off intra- or intermolecuiarly or by reaction with other formaldehyde molecules, thus allowing a wide variety of formaldehyde releasing compounds to be obtained (see Fig. 24). 

Probably the first synthesized formaldehyde releasing compound is hexamethylenetetramine (HTA) which was obtained in 1860 from the condensation of ammonia and formaldehyde according to the reaction pathway illustrated in Fig. 25. 

The efficacy at HTA is based on its formaldehyde content which, however, is only released in acid media. According to its composition HTA is the formaldehyde releasing compound with the highest percentage of bound formaldehyde. As with formaldehyde, HTA preferably attacks bacteria and not mould producing fungi to such an extent. 

The efficacy of iV-(3-chloroallyl)-hexaminium chloride covers a broad spectrum of bacteria and mould producing fungi, yeasts included. However, the activity against bacteria is more pronounced than that against fungi, characterizing the microbicide as a formaldehyde releasing compound. 

Dihydro-1,3,5-dioxazines are the reaction/condensation products of primary amines with 3 mol of formaldehyde. Although they release a higher quantity of formaldehyde than, for example, 1,3-oxazolidines and are therefore more effective than other formaldehyde releasing compounds they are not of practical importance as microbicides because of their limited stability and very pungent odour. 

The favourable solubility properties combined with low toxicity and good skin compatibility at the dilutions used allow the application of the compound in very different fields of application, mainly as a preservative for functional fluids. Although the hexahydro-l,3,5-tris(2-hydroxyethyl)-j -triazine is a formaldehyde releasing compound it is less pungent. Additionally it is cost effective. Therefore it is not surprising that the compound is the main preservative for lubricoolants estimated market share approximately 50%. 

When compared with other amine based formaldehyde releasing compounds the substance does not offer an advantage with respect to its antimicrobial activity. It is not cost effective and therefore has not gained much importance in practical application, although it is distinguished by favourable solubility properties and a weak odour. 

As the MIC in Table 32 prove, Dazomet has an extraordinary broad spectrum of high activity which covers bacteria including formaldehyde resistant bacteria , fungi and yeasts, indicating that the substance is a very special formaldehyde releasing compound. One finds an explanation by looking at the pattern of synthesis which is reversible that means an intermediate of neutral to alkaline hydrolysis is iV-methyl-dithiocarbamate (see Section 9.9), a known antifungal slimicide. A pH between 4 and 9 is the optimum for Dazomet. 

Generally the activity of formaldehyde releasing compounds is reduced in alkaline media containing ammonia, because of the formation of inactive hexam-ethylene tetramine (Section 3.3.1). In the case of MCA, however, the hexamethylene tetramine formed reacts with MCA or CA to give quaternary hexaminium salts (Sections 3.3.5 and 3.3.6) which are effective, as they release formaldehyde widely independent of pH (see Section 3.3). 

The heterocyclic N,S compounds Dazomet (Section 3.3.16) and Taurolin (Section 3.5.2.) can be regarded as formaldehyde releasing compounds therefore they are listed in Section 3. The A -hydroxymethyl derivative of 2-mercaptobenzothiazole (Section 3.4.10.2) is a formaldehyde releasing compound too and is described under Section 3.4, Reaction products of amides and formaldehydes . 

Proteinaceous glues are in particular sensitive to microbial degradation, e.g. skin, leather, boneglues, casein and albumin solutions. Such preparations are not compatible with aldehydes, e.g. formaldehyde releasing compounds coagulation may occur. 

When selecting appropriate microbicides one should pay attention to the fact that Pseudomonades are generally found in non-protected use-dilutions. Among the microbicides for the protection of MWF formaldehyde releasing compounds represent the majority, although they are less effective against fungi than bacteria. 

In addition, on the extensive use of formaldehyde releasing compounds alone problems may occur with the selection of formaldehyde resistant bacteria (Paulus, 1976). It therefore makes sense to use different types of active ingredients to increase the spectrum of activity or even better, combinations which are characterized by synergistic effects. Fungicides are especially suitable for the so-called bioresistant metal working fluids. 

Paulus, W. (1976). Problems encountered with formaldehyde releasing compounds used as preservatives in aqueous systems, especially lubricoolants. Possible solutions to the problems. In Proceedings of the 3rd Int. Biodegrad. Symp., eds. J. M. Sharpley A. M. Kaplan, Applied Science Publishers, London, pp. 1075-82. 

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