Toxicokinetic study of pyrrole adducts and its potential application for biological monitoring of 2,5-hexanedione subacute exposure.
OBJECTIVE
The formation of pyrrole adducts might be responsible for peripheral nerve injury caused by n-hexane, but there is not an effective biomarker for monitoring occupational exposure of n-hexane. The current study was designed to investigate the changes of pyrrole adducts in serum and urine of rats exposed to 2,5-hexanedione (2,5-HD) and analyze the correlation between pyrrole adducts and 2,5-HD.


METHODS
Two groups of male Wistar rats (n = 8) were administered a single dose of 200 and 400 mg/kg 2,5-HD (i.p.), and another two groups (n = 8) were given daily dose of 200 and 400 mg/kg 2,5-HD (i.p.) for 5 days. Pyrrole adducts and 2,5-HD in serum and urine were determined, at different time points after dosing, using Ehrlich’s reagent and gas chromatography, respectively.


RESULTS
The levels of pyrrole adducts in serum accumulated in a time-dependant manner after repeated exposure to 2,5-HD, while pyrrole adducts in urine, and 2,5-HD in serum and urine were kept stable. The half-life times (t1/2) of 2,5-HD and pyrrole adducts in serum were 2.27 ± 0.28 and 25.3 ± 3.34 h, respectively. Furthermore, the levels of pyrrole adducts in urine were significantly correlated with the levels of 2,5-HD in serum (r = 0.736, P < 0.001) and urine (r = 0.730, P < 0.001), and the levels of pyrrole adducts in serum were correlated with the cumulative dosage of 2,5-HD (r = 0.965, P < 0.001).


CONCLUSIONS
The results suggested that pyrrole adducts in serum and urine might be markers of chronic exposure to n-hexane or 2,5-HD.
Hong-Yin
HY
Yin
Ying
Y
Guo
Fu-Yong
FY
Song
Tao
T
Zeng
Ke-Qin
KQ
Xie
D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004784:Environmental Monitoring; D006586:Hexanes / Q000378:metabolism / Q000633:toxicity; D006588:Hexanones / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D011758:Pyrroles / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D066007:Toxicokinetics
D015415:Biomarkers; D006586:Hexanes; D006588:Hexanones; D009498:Neurotoxins; D011758:Pyrroles; C026385:n-hexane; C011269:2,5-hexanedione