Prometryn metabolism

On ingestion prometryn metabolizes, producing amine dealkylation and side chain oxidation. It affects the tricarboxylic acid cycle. 

Alkylthiotriazines. In our laboratory we have studied the metabolic fate of 2-(4-ethylamino-6-methylthio- -triazin-2-ylamino)-2-methylpropionitrile (cyanatryn, 1, Fig. 1). This compound is a member of a class of herbicidal -triazines which also includes ametryne, prometryne and terbutryne. We were interested to note ( ) that two of the major metabolites of cyanatryn were the mercapturic acids 2-[A-ethylamino-6-(N-acetylcysteinyl)- -triazin-2-ylamino]-2-methylpropionitrTle (2.1) and its N-de-ethyl derivative (2.2) (Fig. 2). This pathway had not hitherto been reported for this class of compound. 

The triazine herbicides can be divided into four different structural classes chlorotriazines, methylthiotriazines, methoxytriazines, and atypical or asymmetrical triazines. The chlorotriazine group includes atrazine, simazine, pro-pazine, terbuthylazine, and cyanazine. The methylthiotriazine group includes ametryn, prometryn, and terbutryn. The methoxytriazine group will include prometon and secbumeton. Hexazinone and metribuzin were chosen to represent the atypical triazine group. The plant metabolism of the most researched member of each triazine group will be discussed in detail to cover all major biological and chemical transformations reported in the literature. 

Further analysis of celery samples taken from the aforementioned study characterized 14 metabolites. These structures included simple hydroxy-x-triazines (GS-11526, GS-17794, GS-11957, GS-17791, GS-35713, and cyanuric acid), side-chain oxidized hydroxy-x-triazines (MCO-III-25 and MCO-IV-34), oxidized parent metabolites (GS-16141 and GS-16158), and dealkylated fiiiomethyl-x-triazines (GS-11354 and GS-26831). A metabolic pathway for prometryn in celery is illustrated in Figure 7.9. 

Figure 7.9 The metabolic pathway of prometryn in celery (Sanson, 1992).

Sanson, D.R. (1994). 14C-Prometryn Uptake and Metabolism in Greenhouse Grown Cotton. Submitted to USEPA. 

Triazine compounds are generally well absorbed in the gastrointestinal system. When administered by the oral route, the greatest concentrations of prometryn are found in the blood, spleen, and lungs. Dermal absorption is relatively high, with 7-15% of the material applied to skin being absorbed. Prometryn is excreted in urine or feces within 72 h. It is extensively metabolized, with less than 2% of the parent material appearing in the urine or feces. 

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