Metabolic aspects of the toxicology of mixtures of parathion, toxaphene and/or 2,4-D in mice.
The effects of mixtures of parathion (PA;5 mg kg-1), toxaphene (TOX; 50 mg kg-1)and/or 2,4-dichlorophenoxyacetic acid (2,4-D; 50 mg kg-1) on the hepatic mixed-function oxygenase (MFO) system were studied in ICR male mice (21-24 g) by oral intubation daily for 7 days. In general, TOX and TOX-containing mixtures were found to induce the metabolism of amidopyrine (21-52%), aniline (58-72%), phenacetin (239-307%), pentobarbital (104-148%) and benzo[a]pyrene (143-304%) in the 9000 g liver supernatants and to increase the hepatic cytochrome P-450 contents (57-80%). Furthermore, the TOX pretreatment was effective in enhancing the biotransformation of PA or paraoxon (PO) in the supernatants. This enhancement was not altered significantly by 5 mM EDTA. Although TOX increased the aliesterase activity in the serum and liver homogenates and supernatants by 31-158%, the activity of paraoxonase was not affected in these preparations. The TOX-induced increase in the metabolism of PA or PO was, at least in part, associated with the MFO system, and paraoxonase did not have significant involvement in the increase. These findings suggest that the toxicity of the PA + TOX mixture would be lower than that of PA, as TOX has the ability to increase the biotransformation of PA, as well as of PO, and the levels of aliesterase, thereby providing a pool of noncritical enzymes for the binding of PO. Because of these properties of TOX, it is anticipated that the toxicity of the PA + TOX + 2,4-D mixture also would be lower than that of PA.
Chaturvedi
A K
AK
Department of Pharmaceutical Sciences/Toxicology, North Dakota State University College of Pharmacy, Fargo 58105.
Kuntz
D J
DJ
Rao
N G
NG
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D043303:Aryldialkylphosphatase; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010261:Paraoxon / Q000378:metabolism; D010278:Parathion / Q000633:toxicity*; D010424:Pentobarbital / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D014112:Toxaphene / Q000633:toxicity*
D015084:2,4-Dichlorophenoxyacetic Acid; D010278:Parathion; D014112:Toxaphene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D010744:Phosphoric Monoester Hydrolases; D043303:Aryldialkylphosphatase; D010424:Pentobarbital; D010261:Paraoxon