Introduction Trimethylphosphate ( T M P ) w a s i n t r o d u c e d as a f u e l a d d i t i v e f o r a l t e r i n g t h e e f f e c t s o f e n g i n e d e p o s i t s in 1 9 4 7 . I t is u s e d m a i n l y as a g a s o l i n e a d d i t i v e f o r c o n t r o l l i n g s u r f a c e i g n i t i o n a n d s p a r k - p l u g f o u l i n g [ 1 9 ] . I n i n d u s t r y , i t is u s e d as a m e t h y l a t i n g a g e n t [ 3 ] a n d a l s o as a c a t a l y s t in t h e p r e p a r a t i o n o f r e s i n s a n d p o l y m e r s . A l s o , i t is e m p l o y e d as a f l a m e r e t a r d a n t in p a i n t s a n d p o l y m e r s [19]. Chemical and physical properties Trimethylphosphate is t h e t r i m e t h y l e s t e r o f p h o s p h o r i c a c i d . I t h a s a m o l e c u l a r w e i g h t o f 1 4 0 . 0 9 . I t is a l i q u i d a t r o o m t e m p e r a t u r e , is f r e e l y s o l u b l e i n w a t e r , a n d is s t a b l e i n a q u e o u s s o l u t i o n [ 2 2 ] .
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TMP and other phosphoric acid esters have been reported to react with DNA by Rozenkranz and Rosenkranz [ 28]. This was demonstrated by a reduction in the sedimentation coefficient after incubation of calf-thymus DNA with the esters. Ehrenberg et al. [11] demonstrated that TMP has approximately the same substrate constant as dimethylsulfate, methyl methanesulfate (MMS) and methyl bromide, although TMP is less reactive than the other three methylating compounds. In a study of alkylating activity of paired compounds, Bedford [2], reported that TMP is more reactive than triethylphosphate and the mutagenicity in Saccharomyces cerevisiae parallels the chemical reactivity. Biotransformation Jones, using 3:P-labelled TMP was able to demonstrate the presence of dimethylphosphate (DMP) in the urine of mice and rats treated orally or intraperitoneally [21]. Studies of 3:p-labelled DMP show that it is excreted unchanged and does n o t appear to be further metabolized to mono-alkyl phosphate or phosphoric acid [20,21]. Studies with [14C]TMP revealed two additional urinary metabolites, S-methylcysteine and its N-acetate. This indicates that TMP acts in this instance in an alkylating capacity [21]. In vitro, TMP reacts with glutathione to produce DMP and S-methylglutathione which is the in vivo precursor of S-methylcysteine [21] (Fig. 1).