Monitoring exposure to 4,4'-methylene-bis(2-chloroaniline) through the gas chromatography-mass spectrometry measurement of adducts to hemoglobin.
4,4'-Methylene-bis(2-chloroaniline) (MOCA) is widely used as a curing agent in the plastics industry. The determination of the covalently bound reaction products to hemoglobin (Hb) has been investigated as a biomonitoring method for occupational exposure to this potential human carcinogen. Initial studies using the 14C-ring-labeled MOCA showed that 24 hr after a single IP dosage to rats (3.74 mumole/kg), 0.08% of the administered dose was adducted to the Hb, and base hydrolysis liberated 38% of the bound radioactivity. The only product released on hydrolysis was the parent diamine. A specific and sensitive assay procedure using capillary gas chromatography-mass spectrometry has been developed for determining the base-released MOCA adduct down to levels of 20 pmole/g Hb. This method has been used to establish a linear dose-response relationship in IP dosed rats between production of the adduct and dose of MOCA (3.74-44.94 mumole/kg). It is proposed to use analysis of the Hb adduct as a dosimeter for industrial workers exposed to MOCA.
Bailey
E
E
MRC Toxicology Unit, Carshalton, Surrey, UK.
Brooks
A G
AG
Farmer
P B
PB
Street
B
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects*; D008753:Methylenebis(chloroaniline) / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
D006454:Hemoglobins; D008753:Methylenebis(chloroaniline)