Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride.
OBJECTIVE
To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations.


METHODS
Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS).


RESULTS
During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor.


CONCLUSIONS
The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.
de Rooij
B M
BM
Leiden-Amsterdam Centre for Drug Research (LACDR), Department of Pharmacochemistry, Free University, The Netherlands.
Boogaard
P J
PJ
Commandeur
J N
JN
van Sittert
N J
NJ
Vermeulen
N P
NP
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine*; D000328:Adult; D000395:Air Pollutants, Occupational / Q000652:urine*; D000498:Allyl Compounds / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D004784:Environmental Monitoring; D005737:Garlic / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010946:Plants, Medicinal; D012044:Regression Analysis; D012907:Smoking / Q000378:metabolism
D000395:Air Pollutants, Occupational; D000498:Allyl Compounds; D015415:Biomarkers; D003404:Creatinine; C001423:S-(3-hydroxypropyl)cysteine N-acetate; C023698:allyl chloride; D000111:Acetylcysteine