HL Deb 09 May 1996 vol 572 cc25-6WA
The Countess of Mar

asked Her Majesty's Government:

Whether, they regard the "hen test" as a reliable predictor of irreversible neuropathy caused by organophosphates.

Baroness Cumberlege

The test in hens, as done according to modern protocols (e.g. Organisation for Economic Co-operation and Development guidelines) is the most satisfactory test generally availablefor the prediction of ability to produce organophosphate-induced delayed peripheral neuropathy. Hens are more sensitive to the development of the syndrome than laboratory rodents.

The Countess of Mar

asked Her Majesty's Government:

Whether they are satisfied that studies of long-term exposure to organophosphates in animals may confidently be extrapolated to humans.

Baroness Cumberlege

Some caution is necessary in extrapolating animal studies to humans. It is important to consider factors such as metabolism and pharmacokinetics when making such extrapolations. The expert members of the Government's advisory committees and the department's professional staff are aware of these constraints when considering data from studies before advising the Government.

The Countess of Mar

asked Her Majesty's Government:

Whether it is necessary for organophosphates to age before neuropathies result.

Baroness Cumberlege

The term aging refers to the enzyme neuropathy target esterase (NTE) not to organophosphates. The production of organophosphates-induced delayed peripheral neuropathy (OPIDN) appears to be associated with but not necessarily caused by phosphorylation, with consequent inhibition of NTE. OPIDN appears to occur only when inhibition of NTE is greater than 70 per cent. and this is followed by monodealkylation (aging). There is some evidence that the underlying mechanism may be different with some phosphoramidates—for example, the phosphorothioamidate pesticide methamidophos; with this substance, at high doses, aging does not seem to be obligatory for the development of OPIDN.

The Countess of Mar

asked Her Majesty's Government:

What is known about the effects of exposure to organophosphates in humans upon enzymes other than neuropathy target esterase (NTE).

Baroness Cumberlege

The acute effects of the organophosphates are caused by the ability of these compounds to inhibit various esterases, in particular acetylcholionesterase. Some, if not all, organophosphates have non-anticholinesterase effects; diisopropyl phosphorofluoridate (DFP) influences dopaminergic and somatostatinergic pathways in the rat and leptophos affects Gamma amino butyric acid (GABA) regulated chloride channels, as may sarin. Furthermore, parathion, parathion-methyl and malathion affect camodulin-dependent phosphodiesterase activity.