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Quantification of haemoglobin binding of 4,4′-methylenebis(2-chloroaniline)(MOCA) in rats

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Abstract

4,4′-Methylenebis(2-chloroaniline) (MOCA) is used as a curing agent in the production of polyurethane. MOCA is carcinogenic in experimental animals. Haemoglobin adducts have been proposed as dosimeters of aromatic amines for biological monitoring. A quantitative method to determine the adduct has now been worked out in female Wistar rats dosed per os with 3.82, 14.2 and 16.2 μmol/kg14C-ring labeled MOCA or 0.25 and 0.50 mmol/kg unlabeled MOCA. MOCA bound in decreasing amounts to DNA, RNA and proteins of the lung, liver and kidney. Fractions of 0.19% and 0.026% of the dose were bound to the blood proteins haemoglobin and albumin, respectively. MOCA released by hydrolysis from haemoglobin was determined by HPLC with electrochemical detection or by GC-MS. Albumin did not form any hydrolysable adducts with MOCA.

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Abbreviations

DCBZ:

3,3′-dichlorobenzidine

DMBZ:

3,3′-dimethyl-benzidine

MOCA:

4,4′-methylenebis(2-chloroaniline)

TFA:

trifluoroacetic acid anhydride

PFPA:

pentafluoropropionic acid anhydride

TFA-MOCA:

N,N′-ditrifluoroacetyl-MOCA

TFA-DCBZ:

N,N′-ditrifluoroacetyl-DCBZ

Ac-MOCA:

N-acetyl-MOCA

DiAc-MOCA:

N,N′-diacetyl-MOCA

NCI:

negative chemical ionisation

EI:

electron impact ionisation

SIM:

single ion monitoring

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  1. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacherstrasse 9, 8700, Würzburg, Federal Republic of Germany

    G. Sabbioni & H. -G. Neumann

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  1. G. Sabbioni
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  2. H. -G. Neumann
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Sabbioni, G., Neumann, H.G. Quantification of haemoglobin binding of 4,4′-methylenebis(2-chloroaniline)(MOCA) in rats. Arch Toxicol 64, 451–458 (1990). https://doi.org/10.1007/BF01977626

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  • DOI: https://doi.org/10.1007/BF01977626

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