Sulphate esters, toxicity

In humans mercapturic acid formation appears less significant than detoxification pathways involving glucuronide or sulphate ester formation, but is of considerable importance in other species. Halobenzenes which can cause liver damage lead to mercapturic acid formation in the rat, while non-toxic compounds such as /Mlibromobenzene do not. Such facts strongly support the idea that this pathway has a detoxification role. 

Of these esters, methyl sulphuric acid and dimethyl sulphate were employed as war gases. They have great toxic power and act on the respiratory passages and on the skin. 

In class B are placed all simple esters, CHjF CO i , of fluoro-aoetic acid, where iZ = Me, Et, Pr , Pr , Ph, etc. When substitution takes place in the a-hydrogen atoms, e.g. in methyl a-fluoropropionate or a-fluoroisobutyrate, then the compound is devoid of toxicity. This indicates the importance of the unsubstituted fluoromethyl group. On pp. 125 et seq. it was shown that fluoroacetamide and a variety of substituted amides such as CHjF CO NH CHg CHjCl were, molecule for molecule, equally toxic with fluoroacetic acid and produced the same symptoms. The 2 chloroethyl group therefore contributed nothing appreciable to the toxicity of the molecule. The majority of the esters of fluoroethanol showed the toxicity of the parent alcohol, e.g. 2-fluoroethyl chlorosulphonate, CHgF CHg O SOjCl, di-(2-fluoroethyl) sulphate and 2-fluoroethylglycine hydrochloride. 

About the middle of the nineteenth century, the use of certain phosphorus compounds (rather than the element) became the vogue. The laxative properties of sodium phosphates were recognised and in the same period hypophosphites (as Na, Mg or Ca salts) were introduced for the treatment of neurasthenia and other nervous deficiencies. These were all considerably less toxic than the element itself and were followed by glycerophosphates (as Na, Ca and other salts) which were believed to function as brain nutrients or nerve tonics . The use of hypophosphites and glycerophosphates persisted well into the twentieth century, but they are now considered to be of very limited value for these purposes. A syrup of phosphorus , described in British Pharmacopea 1885, contained phosphoric acid, sodium phosphate and iron sulphate among other ingredients. Commercial exploitation of products of this kind was inevitable (Hgure 12.22). Modem dietary supplements are often based on collections of vitamins which usually include Bg and B,2. These two vitamins form part of phosphate ester enzymes (e.g. Equation ll.lOSj). 

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