Metabolism of propachlor

Figure 11. Metabolism of propachlor to an Fi-malonylcysteine conjugate in soybean root. Soybeans treated with [ C-carbonyl] propachlor were harvested after 4 and 21 days. The glutathione and y-glutamylcysteine conjugates were identified by HPLC and the S-malonylcysteine conjugate was identified by the MS of the...

Nonpolar methylene chloride-soluble residues. Pentachloro-thloanisole and pentachlorothioanlsole sulfoxide were present in the nonpolar methylene chloride-soluble fraction from each of the plant systems examined (Figure 14). In addition, pentachloro-thiophenol was detected in some of these extracts. Pentachloro-thioanisole has been reported as an important residue of PCNB in almost every biological system that has been examined for PCNB metabolism and pentachlorothlophenol has also been reported as a residue in several of these systems S). The formation of these residues from S-(PCP)GSH via the pathway shown in Figure 16 was considered highly probable. Recent vivo studies indicated that such a system also operates in mammals in the metabolism of propachlor ( ) and pentachlorothioanlsole (20). vitro... 

Species differences in the metabolism of propachlor are summarized in Table II. All species studied metabolized propachlor in the MAP. Obvious, but unexplained differences are that the rat excreted no cysteine conjugate and the chicken formed no methylsulfonyl-containing metabolites. The absence of methylsulfonyl formation by chickens is thought due to the low biliary secretion of first pass metabolites. The ruminant (sheep) excreted large amounts of cysteine conjugate in urine which is also not explained. We do not know if the intestinal flora are involved in the formation of the methylsulfonyl acetanilides isolated from sheep urine. 

Table II. Metabolism of propachlor in various species and antibiotic treated pigs...

Propachlor is almost completely metabolised in plants in 5 days. It is only weakly adsorbed by the soil and is rapidly degraded, about 94% microbially and 6% chemically. Jaworski and Porter (1965) and Jaworski (1969) studied the metabolism of propachlor in maize and soybean. The sole metabolite found was a water-soluble acid compound, giving N-isopropylaniline after alkaline hydrolysis. The metabolite produced 2-hydroxy-N-isopropylanilide on acid hydrolysis. Presumably, the active chlorine atom of propachlor is transferred during metabolism to some endogenous nucleophyle, with which it forms a glucoside conjugate. This conjugate is fairly stable and presumably not phytotoxic. 

Lamoureux and Davison (1975), investigating the metabolism of propachlor in rats, found that here too the mercapturic acid pathway plays an important role. Rats treated with -propachlor excerted 20% of the dose in the form of mercapturic acid conjugate 24 hours after treatment ... 

The complexity of the metabolism of alachlor, acetochlor, butachlor, and propachlor has led to the development of degradation methods capable of hydrolyzing the crop and animal product residues to readily quantitated degradation products. Alachlor and acetochlor metabolites can be hydrolyzed to two major classes of hydrolysis products, one which contains aniline with unsubstituted alkyl groups at the 2- and 6-positions, and the other which contains aniline with hydroxylation in the ring-attached ethyl group. For alachlor and acetochlor, the nonhydroxylated metabolites are hydrolyzed in base to 2,6-diethylaniline (DBA) and 2-ethyl-6-methylaniline (EMA), respectively, and hy-droxylated metabolites are hydrolyzed in base to 2-ethyl-6-(l-hydroxyethyl)aniline (HEEA) and 2-(l-hydroxyethyl)-6-methylaniline (HEMA), respectively. Butachlor is metabolized primarily to nonhydroxylated metabolites, which are hydrolyzed to DEA. Propachlor metabolites are hydrolyzed mainly to A-isopropylaniline (NIPA). The base hydrolysis products for each parent herbicide are shown in Eigure 1. Limited interference studies have been conducted with other herbicides such as metolachlor to confirm that its residues are not hydrolyzed to the EMA under the conditions used to determine acetochlor residues. Nonhydroxylated metabolites of alachlor and butachlor are both hydrolyzed to the same aniline, DEA, but these herbicides are not used on the same crops. 

Photolytic. When propachlor in an aqueous ethanolic solution was irradiated with UV light (>, = 290 nm) for 5 h, 80% decomposed to the following cyclic photoproducts W-isopropyloxindole, W-isopropyl-3 hydroxyoxindole, and a spiro compound. Irradiation of propachlor in an aqueous solution containing riboflavin as a sensitizer resulted in completed degradation of the parent compound. 3-Hydroxypropachlor was the only compound identified in trace amounts which formed via ring hydroxylation (Rejtb et al, 1984). Hydrolyzes under alkaline conditions forming W-isopropylaniline (Sittig, 1985) which is also a product of microbial metabolism (Novick et al., 1986). 

Lamoureux, G.L., Stafford, L.E., and Tanaka, F.S. Metabolism of 2-chloro-lV-isopropylacetanilide (propachlor) in the leaves of corn, sorghum, sugarcane, and barley, /. Agric. Food Chem., 19(2) 346-350, 1971. 

Novick, N.J., Mukherjee, R., and Alexander, M. Metabolism of alachlor and propachlor in suspensions of pretreated soils and in samples from ground water aquifers, / Agrlc. Food Chem., 34(4) 721-725, 1986. 

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

Bakke, J. E., G. L. Larsen, and P. W. Aschbacher. The Effect of Oral Li neomycin on the Metabolism of the Herbicide Propachlor by the Pig. American Society of Animal Science. 1980. (Abstract). 

Propachlor Is metabolized by this route In both a resistant and a susceptible species (Equation 16). Glutathione conjugation of propachlor occurs very rapidly Un vitro in the absence of GST enzymes (78) and It Is not clear whether differences In GSH and/or GST concentratlois influence the selectivity of propachlor and related herbicides. The concentration of GSH In higher plants Is estimated... 

Propachlor, alachlor, acetochlor, and butachlor degrade readily and extensively in soil mainly through displacement of chlorine followed by further metabolism to numerous... 

The oral administration of antibiotics resulted in the production of germfree characteristics with respect to propachlor metabolism in rats ( ) and pigs (31), i.e. no 2-methylsulfonyl acetanilides were formed and only MAP metabolites were excreted. This observation may have economic implications. It is possible that the growth stimulation observed upon incorporation of antibiotics into animal feed could be effected by the suppression of such mechanisms. This could be accomplished either by the prevention of the metabolic formation of new xenobiotics of unknown biological activities or by the conservation of detoxication energy or both. 

Propachlor is absorbed through the gastrointestinal tract, through intact skin, and through the respiratory system after inhalation of dust or spray mist. It is metabolized via the mercapturic acid pathway. The major fecal metabolite is a cysteine conjugate. Rats administered propachlor orally excreted 98.6% of the dose in the urine and feces within 48 h. Approximately 50% is excreted as metabolites through urine or feces within 24 h. 

Propachlor and related o-chloroacetamlde herbicides are metabolized by nucleophilic displacement of a chloro-group with GSH (82. 

Several xenobiotics that are metabolized by GSH conjugation In plants, Including atrazine, propachlor, and PCNB, produce significant levels of bound residue (15). It appears that the bound residue may be formed from the GSH pathway with either a cysteine conjugate or a thiol as a precursor 1 5). The chemical nature of these bound residues has not been determined. 

Other representative pesticides that have also been shown to be mineralized include glyphosate, parathion, carbaryl, EPTC, isofenphos, and propachlor. Pesticides that are susceptible to mineralization are not typically found in, or considered to be a threat to, groundwater supplies because of their rapid degradation, ie, nonpersistence. Microorganisms can evolve, that is, develop metabolic pathways for the mineralization of previously persistent compounds. For example, there have been several reports documenting the existence of atrazine-mineralizing microoiganisms (21). 

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