Interaction between .gamma.-hexachlorocyclohexane and the gastrointestinal microflora and their effect on the absorption, biotransformation, and excretion of parathion by the rat

Chadwick, Robert W.; Copeland, Matthew F.; Froehlich, Ritchie; Cooke, N.; Whitehouse, Douglas A.

doi:10.1021/jf00124a013

Cited by 12 publications

(4 citation statements)

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“…/?-Glucuronidase ( E C 3.2.1.31) activity was calculated as the amount of p-nitrophenol released from the hydrolysis of p-nitrophenyl-fi-D-glucuronide tissue g h -Dechlorinase (EC 3.8.1.1) and dehydrochlorinase (EC 4.5.1.1) activity were determined by analysing the amounts of p-p'-DDD and p-p'-DDE produced from the p-p'-DDT tissue g-' h-' . The derivatization procedures used in this assay were described by Chadwick et al (1984).…”

Section: Enzyme Assaysmentioning

confidence: 99%

“…Apart from their physiologic functions, intestinal bacteria may be involved in the initiation of colonic carcinogenesis (Goldin and Gorbach 1976;Manning et al 1986;Hill 1987). For example, the biotransformation and metabolism of parathion and the genotoxicity of 2,6-dinitrotoluene are mediated by intestinal bacteria (Chadwick et al 1984;George et al 1992). In addition, potentiation of genotoxicity of 2,6-dinitrotoluene by pentachlorophenol or Aroclor 1254 via metabolic activation by intestinal bacteria has been reported (Chadwick et al 1990a(Chadwick et al , 1993.…”

Section: Introductionmentioning

confidence: 99%

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Microbial succession and intestinal enzyme activities in the developing rat

Chang

Chadwick

Allison

et al. 1994

Journal of Applied Bacteriology

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The succession of gut bacteria and selected intestinal enzyme activities in developing 7-35-d-old rats was studied. Aerobes and anaerobes were identified as members of four broad major bacterial groups, i.e. Gram-positive rods, Gram-positive cocci, Gram-negative rods and obligate anaerobes. The enzyme activities of nitro and azo reductases, beta-glucuronidase, dechlorinase and dehydrochlorinase were determined by anaerobic incubation of intestinal homogenates with 3,4-dichloronitrobenzene, methyl orange, p-nitrophenyl-beta-D-glucuronide, and p,p'-DDT respectively. Nitroreductase and azo reductase activities increased significantly with the appearance of anaerobes in the large intestine. No increase in either nitroreductase or azo reductase activities in the small intestine was found. The early and high level of beta-glucuronidase activity in the small and large intestines coincided with high numbers of coliforms recovered in 7 and 14 d animals. Dehydrochlorinase activity appeared early but was undetectable at both 21 and 28 d. Its activity increased at 35 d. Dechlorinase activity was variable in development. The rapid changes in the microbial flora and intestinal enzyme activities may influence the susceptibility of pre-pubescent rats to a variety of toxicants. Therefore, age-dependent toxicity may be important in the risk assessment of some environmental chemicals.

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Section: Enzyme Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microbial succession and intestinal enzyme activities in the developing rat

Chang

Chadwick

Allison

et al. 1994

Journal of Applied Bacteriology

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“…In any event, the present data indicate that methyl parathion administered orally is readily absorbed, but exhibits a significant first pass effect. High oral absorption of methyl parathion and parathion in rats, rabbits and dogs has been reported previously [3,6,27].…”

Section: Discussionmentioning

confidence: 59%

Pharmacokinetics of Methyl Parathion: A Comparison following Single Intravenous, Oral or Dermal Administration

et al. 2002

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Assessment of the risks posed by the residential use of methyl parathion requires an understanding of its pharmacokinetics after different routes of exposure. Thus, studies were performed using adult female rats to define the pharmacokinetic parameters for methyl parathion after intravenous injection and to apply the described model to an examination of its pharmacokinetics after single oral or dermal exposure. The pharmacokinetics of methyl parathion after intravenous administration (1.5 mg/kg) were best described by a three-compartment model; the apparent volume of the central compartment was 1.45 liters/kg, clearance was 1.85 liters/h/kg and the terminal half-life was 6.6 h with an elimination constant of 0.50 h^–1. The apparent oral absorption coefficient for methyl parathion (1.5 mg/kg) was 1.24 h^–1, and its oral bioavailability was approximately 20%. The latter likely includes a significant first pass effect. Concentrations of methyl parathion increased during the initial 10–60 min and then declined during the next 15–36 h. After dermal administration (6.25–25 mg/kg), methyl parathion concentrations peaked within 12–26 h and then declined dose dependently. The apparent dermal absorption coefficient was approximately 0.41 h^–1, and only two pharmacokinetic compartments could be distinguished. In conclusion, the pharmacokinetics of methyl parathion are complex and route dependent. Also, dermal exposure, because of sustained methyl parathion concentrations, may pose the greatest risk.

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“…It had been previously demonstrated that pretreatment of rats with 20 mg/kg lindane, an organochlorine insecticide, reduced both the estimated absorption rate of parathion from the GI tract and the excretion of the hydrolysis product p-nitrophe-no1 [41]. This investigation showed that lindane pretreatment stimulated the conversion of parathion to aminoparathion in the intestinal tract.…”

Section: Effect Of Environmental Chemicalsmentioning

confidence: 56%

Effects of age, species difference, antibiotics and toxicants on intestinal enzyme activity and genotoxicity

Chadwick

George

Kohan

et al. 1993

Enviro Toxic and Chemistry

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Altered intestinal enzyme activity significantly affects the biotransformation and toxicity of many xenobiotics. This article summarizes research, supported by the U.S. Air Force Bioenvironmental Hazards Research Program, that employs a novel gas‐liquid chromatographic assay to investigate the effects of age, species difference, antibiotics, and environmental chemicals on enzyme activity in various regions of the intestinal tract. Significant research findings include the following: (a) age‐dependent alterations in enzyme activity in the gastrointestinal (GI) tract of the developing animal that suggest a changing susceptibility to toxicants during this period; (b) discovery of previously unreported mucosal enzymes in the small intestine that are present in germ‐free rats and are not susceptible to antibiotics; (c) markedly greater intestinal nitroreductase activity and significantly higher bioactivation of the procarcinogen 2,6‐dinitrotoluene (DNT) in CD‐1 mice than in Fischer 344 rats; (d) significantly altered intestinal enzyme activity in rats pretreated with lindane, pentachlorophenol, 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T), or Aroclor 1254; (e) potentiated DNT genotoxicity by Aroclor 1254 and pentachlorophenol pretreatment; and (f) a transient antagonism of DNT genotoxicity by 2,4,5‐T pretreatment. Enzyme activity in the small intestine may have greater toxicological importance than previously thought in the biotransformation of environmental chemicals and as an indicator of change in the microbial flora.

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Interaction between .gamma.-hexachlorocyclohexane and the gastrointestinal microflora and their effect on the absorption, biotransformation, and excretion of parathion by the rat

Cited by 12 publications

References 11 publications

Microbial succession and intestinal enzyme activities in the developing rat

Microbial succession and intestinal enzyme activities in the developing rat

Pharmacokinetics of Methyl Parathion: A Comparison following Single Intravenous, Oral or Dermal Administration

Effects of age, species difference, antibiotics and toxicants on intestinal enzyme activity and genotoxicity

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