Identification of Exposure Pathways for Opioid Narcotic Analgesics in Pharmaceutical Production Workers

Abstract

The protection of workers from the potential harmful effects of active pharmaceutical ingredients (APIs) poses a significant challenge for the drug manufacturing industry. The actual pathways through which pharmaceutical production workers are exposed to potent drugs and the processes resulting in actual uptake are up till now virtually unknown. In this study, a detailed exposure assessment survey was conducted in a pharmaceutical 'primary manufacturing' production facility during which environmental and biological exposure monitoring for potent opioid narcotic drugs was performed. On the occasion of multiple consecutive production days, personal half-shift air samples were collected and hand wipes were taken at the end of each half-shift and analysed for fentanyl. All environmental samples showed detectable amounts of fentanyl (>0.1 ng per sample), indicating a potential for both inhalation and dermal exposure. Spatial distribution of fentanyl dermal contamination was further investigated by means of patch samplers placed on five anatomical regions of the body. Body locations showing the highest level of fentanyl contamination were identified as the hands, the neck and lower arms. The effective uptake of fentanyl was demonstrated by the detection of this opioid in urine samples of the workers involved. Individual and group-level analysis of combined external and internal fentanyl exposure measures revealed a positive and significant correlation between fentanyl hand exposure and urinary excretion, while it seemed that the effect of inhalation exposure was largely due to its correlation with dermal exposure. The results of the established individual linear and mixed effects models strongly suggest that in most workers the dermal pathway is actually the primary route of fentanyl exposure.

Evaluation of occupational exposures to illicit drugs at controlled substances laboratories.

“…In general, personal fentanyl and cocaine air exposures in this evaluation were much lower than those measured in similar studies or evaluations [Le et al 1992;Gehlhausen et al 2003;Van Nimmen et al 2006]. None of the interviewed employees reported any symptoms related to handling cocaine or opioids at work, and OSHA 300 Logs revealed only one employee with reported symptoms possibly associated with PCP.…”

“…The geometric mean exposure we measured (0.007 µg/m 3 ) was also much lower than the geometric mean in this study of pharmaceutical employees. None of the full-shift fentanyl exposures exceeded an occupational exposure limit established by a fentanyl manufacturing company of 0.1 µg/m 3 [Van Nimmen et al 2006].…”

“…Table C2 contains the TWA full-shift concentrations for all the participating chemists. None of the full-shift fentanyl exposures exceeded an occupational exposure limit established by a fentanyl manufacturing company of 0.1 µg/cubic meter (m 3 ) [Van Nimmen et al 2006]. The other analytes, cocaine, heroin, and methamphetamine, do not have established occupational exposure limits.…”

“…In one study of employees who manufactured fentanyl, full-shift TWA personal air exposures to fentanyl were 0.5-7,310 ng/m 3 (0.0005-7.31 µg/m 3 ), with a geometric mean of 40 ng/m 3 (0.04 µg/m 3 ) [Van Nimmen et al 2006]. The majority of these pharmaceutical employee exposures were much higher than full-shift personal exposures we measured on chemists by several orders of magnitude.…”

Evaluation of occupational exposures to illicit drugs at forensic sciences laboratories.

“…Table C4 contains the TWA full-shift concentrations for all participating employees. None of the full-shift fentanyl exposures exceeded an occupational exposure limit established by a fentanyl manufacturing company (0.1 µg per cubic meter) [Van Nimmen et al 2006]. The other analytes, cocaine, heroin, and methamphetamine do not have established occupational exposure limits.…”