Electrophysiological and Biochemical Effects of Single and Multiple Doses of the Organophosphate Diazinon in the Mouse

Blaquiere, G.E. De; Waters, Laura; Blain, Peter G.; Williams, Faith M.

doi:10.1006/taap.2000.8960

Cited by 44 publications

(20 citation statements)

References 29 publications

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“…The similarity of the profile of AChE inhibition in the marmoset to that reported in humans following diazinon intoxication (FAO/WHO, 1966), along with the appropriateness of this species for behavioural (Roberts, 1996) and sleep studies (Crofts et al, 2001), raises the confidence with which the data obtained here can be extrapolated to humans. This is in marked contrast to studies in rodents where peak inhibition of AChE occurs at 3 h (Wu et al, 1996;de Blaquiere et al, 2000) and markedly different sleep patterns are seen (Ball, 1992). Additionally, data from non-human primate behavioural testing can be considered to be more comparable to humans than data from rodents because their cognitive capabilities and cortical-subcortical relationships are much more similar (Everitt et al, 1988;Roberts, 1996).…”

Section: Discussioncontrasting

confidence: 65%

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Muggleton¹,

Smith

Scott

et al. 2005

J Psychopharmacol

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The long-term sequelae of exposure to low doses of organophosphate compounds are ill defined, with effects variously reported on a range of indices of central nervous system functions such as sleep, cognitive performance and electroencephalogram (EEG). These indices were examined in common marmosets exposed to a range of doses of the organophosphorous sheep dip, diazinon. Cognitive performance was assessed by means of elements from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and radiotelemetry techniques were employed to monitor the electrocorticogram and sleep patterns. Data were collected for 12 months following intramuscular administration of a single dose of diazinon (10, 90 or 130 mg.kg (-1)) or vehicle. Although high levels of erythrocyte acetylcholinesterase (AChE) inhibition (up to 82%) and short-term changes in sleep patterns were seen, there was no evidence of biologically significant long-term changes in any measures. The effects of multiple exposures, impurities or mixtures of OP compounds remain to be investigated.

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Section: Discussioncontrasting

confidence: 65%

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Muggleton¹,

Smith

Scott

et al. 2005

J Psychopharmacol

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“…Diazinon is widely used as a pesticide in sheep dip formulations, spray pesticides for household use, and cat flea collars (de Blaquiere et al, 2000; Garfitt et al, 2002). Diazinon is a poor inhibitor of acetylcholinesterase and BChE until it is activated to the oxon.…”

Section: Discussionmentioning

confidence: 99%

Methamidophos, dichlorvos, O‐methoate and diazinon pesticides used in Turkey make a covalent bond with butyrylcholinesterase detected by mass spectrometry

Tacal

Lockridge

2010

J of Applied Toxicology

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Organophosphorus pesticides used most commonly in Turkey include methamidophos, dichlorvos, O-methoate, and diazinon. These toxic chemicals or their metabolites make a covalent bond with the active site serine of butyrylcholinesterase. Our goal was to identify the adducts that result from the reaction of human butyrylcholinesterase with these pesticides. Highly purified human butyrylcholinesterase was treated with a 20-fold molar excess of pesticide. The protein was denatured by boiling and digested with trypsin. MS and MSMS spectra of HPLC-purified peptides were acquired on a MALDI-TOF-TOF 4800 mass spectrometer. It was found that methamidophos added a mass of +93, consistent with addition of methoxy aminophosphate. A minor amount of adduct with an added mass of +109 was also found. Dichlorvos and O-methoate both made dimethoxyphosphate (+108) and monomethoxyphosphate adducts (+94). Diazinon gave a novel adduct with an added mass of +152 consistent with diethoxythiophosphate. Inhibition of enzyme activity in the presence of diazinon developed slowly (15 h), concomitant with isomerization of diazinon via a thiono-thiolo rearrangement. The isomer of diazinon yielded diethoxyphosphate and monoethoxyphosphate adducts with added masses of +136 and +108. MSMS spectra confirmed that each of the pesticides studied made a covalent bond with serine 198 of butyrylcholinesterase. These results can be used to identify the class of pesticides to which a patient was exposed.

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“…2 These neurological effects were different from those associated with the delayed neuropathy known to follow acute poisoning with those organophosphate compounds that were already acknowledged to be neurotoxic and consequently had been banned from use. The new neurotoxic effects in humans ranged from neurobehavioural and electroencephalographic changes to increases in the variability of action potential latencies in skeletal muscles (the “jitter” of neuromuscular transmission measured in humans by single fibre electromyogram (SFEMG)).…”

mentioning

confidence: 93%

Adverse health effects after low level exposure to organophosphates

Blain

2001

Occup Environ Med

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Electrophysiological and Biochemical Effects of Single and Multiple Doses of the Organophosphate Diazinon in the Mouse

Cited by 44 publications

References 29 publications

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets

Methamidophos, dichlorvos, O‐methoate and diazinon pesticides used in Turkey make a covalent bond with butyrylcholinesterase detected by mass spectrometry

Adverse health effects after low level exposure to organophosphates

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