Selecting an appropriate biomonitoring strategy to evaluate dermal exposure to opioid narcotic analgesics in pharmaceutical production workers.
OBJECTIVE
In a follow-up study of previous research, in which exposure pathways for opioid narcotic analgesics were identified in pharmaceutical workers involved in drug synthesis, the current research focused on the selection of an appropriate biomonitoring strategy.


METHODS
Six opioid narcotic production workers were intensively monitored during a (1 week) fentanyl production campaign. A systematic sampling scheme was followed that provided information about hand contamination and biomarker levels at multiple time points.


RESULTS
Linear mixed-effects models, incorporating half-shift and end-of-shift hand contamination levels, showed a positive and significant correlation with fentanyl urinary excretion occurring at many of the 4 h time lags investigated (4-28 h). Optimum model characteristics, including both minimal between- and within-worker variability, were obtained at lag times of 24 h and 20 h, respectively, advocating a pre-shift urine sampling strategy on the following day. In addition, for these lag times the portion of the variability explained by the model was maximal. Furthermore, using a distributed lag model, it was demonstrated that urinary fentanyl levels were positively correlated with hand contamination levels measured at the preceding four 8 h time lags (8-32 h), although statistical significance was only shown for a lag time of 24 h.


CONCLUSIONS
Fentanyl levels in pre-shift urine samples reflect dermal exposure to the compound during the previous day. Thus, in the specific working environment investigated, a biological monitoring protocol evaluating pre-shift urinary fentanyl levels could provide an adequate risk estimate in individual workers.
Van Nimmen
N F J
NF
Katholieke Universiteit Leuven, Department of Occupational, Environmental and Insurance Medicine, Kapucijnenvoer 35/5, Leuven, Belgium.
Poels
K L C
KL
Severi
M J
MJ
Godderis
L
L
Veulemans
H A F
HA
D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity* / Q000652:urine; D000701:Analgesics, Opioid / Q000633:toxicity* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D004345:Drug Industry; D004784:Environmental Monitoring / Q000379:methods; D005283:Fentanyl / Q000633:toxicity* / Q000652:urine; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000633:toxicity* / Q000652:urine; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis; D012869:Skin Absorption
D000395:Air Pollutants, Occupational; D000701:Analgesics, Opioid; D015415:Biomarkers; D009294:Narcotics; D005283:Fentanyl