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2148082 
Journal Article 
Opioids: Occupational Contact Dermatitis And The Local Lymph Node Assay (LLNA) 
Olson, MJ; Guerriero, FJ; Cunningham-Hill, M; Tapscott, N 
2005 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
TOX/5000606 
84 
1-S 
eng 
Allergy to some opioid phenanthrene derivatives, including morphine and codeine, is recognized as a hazard in health care and pharmaceutical workers handling these materials. Retrospective assessment of human cases of occupational allergy by patch test has been used to categorize a limited number of opioids as dermal allergens. However, very little information is available on the use of laboratory assays to prospectively assess the allergenic potential of specific opioids. Recent trends in opioid chemistry suggest that this gap should be addressed in evaluating the potential impact of less well characterized opioids on occupational health. For example, Papaver somniferum (opium poppy) strains have been selectively developed to express high levels of the phenanthrene derivatives thebaine and oripavine as a means to provide raw materials for synthesis of newer medically important opioids. In addition, chemical syntheses yield stable, isolated substances such as 14-hydroxynormorphinone (NHM) from bioactive, native opioids. NHM is non-analgesic and relatively safe to transport and process, but can be readily chemically converted to medically useful opioid antagonists. As an initial step in quantifying the allergenic potential and potency of materials such as NHM, thebaine, and oripavine, we have assessed these materials in the LLNA. In addition, since opioids can trigger histamine release, these materials have been assessed for potential to irritate eye and skin in the GSK tiered worker safety test battery. The LLNA predicts NHM as a sensitizer with concentration-dependent increases3-fold in stimulation index observed at applied concentrations of 10% and 25% and a <3-fold SI at 5%. NHM was nonirritant to skin but was a mild eye irritant. NHM has also been identified recently as a human dermal allergen. Very similar LLNA and dermal/ocular irritation findings for oripavine have also been obtained. In summary, the LLNA used in conjunction with assays for direct irritant potential provides useful data for prospectively assessing occupational hazards of opioids.