Kinetic analysis of the fate of methyl parathion in the dog

Braeckman, René; Godefroot, M.; Blondeel, G. M.; Belpaire, Frans

doi:10.1007/bf00366182

Cited by 19 publications

(7 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The terminal half-life for methyl parathion in female rats estimated here (6.6 days) is less than half of its reported half-life in male rats (approximately 15 days) following oral administration [19]. It also differs substantially from the estimated half-life of methyl parathion in dogs (7.2 h) as well as that of parathion in rats (3.4 h) or rabbits (5.1 h) following intravenous administration [4,16,32].…”

Section: Discussioncontrasting

confidence: 45%

“…ethyl parathion and parathion) in rat [16], dog [3,4,16] or rabbit [32] were best described by multi (two Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

“…Further, a single dermal exposure to methyl parathion can cause sustained inhibition of cholinesterase activity, and repeated dermal exposure can result in impairment of both memory and motor function [26,45]. Pharmacokinetic data for methyl parathion and its metabolites following different routes of exposure, however, are sparse [3,4,11,15,16]. Thus, the present studies were performed to compare the pharmacokinetics of methyl parathion following single intravenous, oral or dermal administration using adult female rats as an experimental model.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 45%

“…ethyl parathion and parathion) in rat [16], dog [3,4,16] or rabbit [32] were best described by multi (two Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Influences on the pharmacokinetics of methyl paraoxon and the activity of acetylcholinesterase follow in turn. Yet, there are only limited data related to methyl parathion with which to predict the potential long-term health risks resulting from a pattern of exposure that occurred with its use in domestic settings [2,7,8,14,16,20,22,36,40]. Also, methyl parathion and other organophosphorus insecticides exhibit a broad range of toxicities and abilities to inhibit acetylcholinesterase [10,11,18,19], making inferences between agents and across species speculative at best.…”

mentioning

confidence: 99%

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

Krämer¹,

Wellman²,

Zhu³

et al. 2002

J Biomed Sci

View full text Add to dashboard Cite

Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30–48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37°C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (≧6 h) and was prolonged (≧48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects.

show abstract

“…The biexponential curve (Figure 7) obtained in most of the iv dose experiments is characteristic of a twocompartment open model which was reported as descriptive of the toxicokinetics of MPT in dogs (Braeckman et al, 1980). The plasma concentration-time data for MPT in goats following iv administration revealed a rapid distribution phase and a slower elimination phase.…”

Section: Discussionmentioning

confidence: 77%