Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat

Chambers, Janice E.; Ma, Tangeng; Boone, J. Scott; Chambers, Howard W.

doi:10.1016/0024-3205(94)00515-x

Cited by 94 publications

(37 citation statements)

References 17 publications

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“…Similarly, cattle weight gain was not significantly reduced by either of the reversible, carbamate-type inhibitors, physostigmine (Haufe 1973) or carbaryl (Khan and Lawson 1965). These comparisons suggest that the degree of cholinesterase inhibition observed during our experiments is within an expected range but that inhibition of plasma cholinesterase need not lead directly to changes in weight gain or feed utilization (Awal 1992;Chambers et al 1994 For personal use only.…”

mentioning

confidence: 59%

“…Diazinon and diazoxon, also both undergo rapid hydrolytic deactivation in cattle blood (Machin et al 1975) and the factors which determine the relative importance of these competing pathways can also influence the development and maintenance of cholinesterase inhibition and toxicity (Chambers et al 1994). Our inability to detect cholinesterase inhibition in cattle fitted with ear tags might then be explained by assuming that release from the tag, rather than percutaneous absorption after topical application, was rate determining.…”

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confidence: 98%

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Weight gain and feed utilization of Hereford steers exposed to diazinon

Danielson¹,

Golsteyn²

1997

Can. J. Anim. Sci.

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Danielson, T. J. and Golsteyn, L. R. 1997. Weight gain and feed utilization in Hereford steers exposed to diazinon. Can. J. Anim. Sci. 77: 181-183. Body weights and feed consumption were monitored in 48 Hereford steers, under feedlot conditions, for 10 wk after exposure to diazinon, an organophosphate insecticide. Experimental design consisted of four complete blocks, each of four treatment groups (positive and negative controls, two insecticidal ear tags and four insecticidal ear tags). Plasma cholinesterase activity was reduced by 50%, 24 h after topical application of diazinon directly to the skin (positive control) but was not reduced after attachment of either two or four insecticidal ear tags per animal. Daily weight gain and feed utilization in control animals, during the 70-d study, were 1.21 ± 0.22 kg d -1 and 0.144 ± 0.007 kg kg -1 (dry matter basis) and were not altered in steers exposed to diazinon.

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confidence: 59%

mentioning

confidence: 98%

Weight gain and feed utilization of Hereford steers exposed to diazinon

Danielson¹,

Golsteyn²

1997

Can. J. Anim. Sci.

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“…However, it is unlikely that individuals expressing the RR protein would be less susceptible to paraoxon toxicity than QQ homozygotes because PON1's overall catalytic efficiency toward this oxon was very poor (Li et al, 2000). It is more likely that carboxylesterases and cholinesterases, which are highly expressed in the liver, would mainly influence removal by covalent binding of the relatively low levels of paraoxon formed following exposure to parathion in vivo (Chambers et al, 1994). In support of this notion, a study by Karanth et al (2001) highlighted the importance of both PON1 and carboxylesterases in the effective detoxification of chlorpyrifos-oxon in contrast to paraoxon that was degraded by carboxylesterases, but not PON1, at biologically relevant concentrations.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between PON1 Phenotype and PON1-192 Genotype in Detoxification of Three Oxons by Human Liver

Mutch¹,

Daly²,

Williams³

2006

Drug Metab Dispos

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ABSTRACT:Phosphorothioate pesticides (OP) such as diazinon, chlorpyrifos, and parathion are activated to highly toxic oxon metabolites by the cytochromes P450 (P450s), mainly in the liver. Simultaneously, the P450s catalyze detoxification of OP to nontoxic dearylated metabolites. The oxon is then detoxified to the dearylated metabolite by PON1, an A-esterase present in the liver and blood serum. The aims of this study were to define the influence of PON1-192 genotype and phenotype on the capacity of human liver microsomes (n ‫؍‬ 27) to detoxify the oxons diazoxon, chlorpyrifos-oxon, and paraoxon. Near physiological assay conditions were used to reflect as closely as possible metabolism in vivo and because the hydrolytic activity of the allelic variants of PON1-192 are differentially affected by a number of conditions. The rates of hydrolysis of diazoxon, chlorpyrifos-oxon, and paraoxon varied 5.7-, 16-, and 56-fold, respectively, regardless of PON1-192 genotype. Individuals with the PON1-192RR genotype preferentially hydrolyzed paraoxon (p < 0.01), and the R allele was associated with higher hydrolytic activity toward chlorpyrifos-oxon, but not diazoxon. There were strongly significant relationships between phenylacetate and paraoxon hydrolysis (p < 0.001) and phenylacetate and chlorpyrifos-oxon hydrolysis (p < 0.001), but not between phenylacetate and diazoxon hydrolysis. These data highlight the importance of PON1 phenotype for efficient hydrolysis of paraoxon and chlorpyrifos-oxon, but environmental and yet unknown genetic factors are more important than PON1-192 genotype in determining capacity to hydrolyze diazoxon.

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“…Shao-Nan and De-Fang (1996) also reported increased malathion toxicity to P.parva in the presence of PBO. (Dauterman, 1976;Kao et al, 1985;Chambers et al, 1994). Hence, the observed increase in acute toxicity of FNT to TPP pre-treated fish may be due to inability of the fish to detoxify FNT.…”

Section: Acute Toxicitymentioning

confidence: 99%

“…According to Chambers et al (1994), phosphrothionate insecticides and their active metabolites can be detoxified by a variety of hepatic mechanisms. This includes P-450-mediated dearylation, phosphorylation of aliesterases (carboxylesterases), catalytic hydrolysis of oxon by A-esterases, glutathion (GSH)-dependent detoxification, etc.…”

Section: Introductionmentioning

confidence: 99%

Acute toxicity and effect of fenitrothion on liver esterase of fish

Sorsa¹

2004

SEJS

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ABSTRACT:The acute toxicity of fenitrothion (FNT) alone and combined with piperonyl butoxide (PBO) or triphenyl phosphate (TPP), and their effect on liver esterase (LE) activity of Gambusia holbrooki, Pseudorasobora parva and Oncorhynchus mykiss was studied in aquaria for 96h. The results indicated that fenitrothion is moderately toxic to the three species of fish tested, the toxicity being highest to O. mykiss followed by P. parva and G. holbrooki. Both FNT concentrations and the exposure time on the activity of LE and FNT (two way ANOVA P<0.05) caused more inhibition in G. holbrooki than P. parva. Pretreating fish with either PBO or TPP changed the acute toxicity level and LE sensitivity compared with those exposed to FNT alone. The acute toxicity level and susceptibility of LE to FNT was found to be inversely related. With additional studies P. parva and G. holbrooki have the potential to be used as bioindicator, and LE as biochemical biomarker of environmental pollution by FNT and other related compounds.

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Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat

Cited by 94 publications

References 17 publications

Weight gain and feed utilization of Hereford steers exposed to diazinon

Weight gain and feed utilization of Hereford steers exposed to diazinon

The Relationship between PON1 Phenotype and PON1-192 Genotype in Detoxification of Three Oxons by Human Liver

Acute toxicity and effect of fenitrothion on liver esterase of fish

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