Evaluation of dermal sensitization to Western Red Cedar extract and abietic acid using the local lymph node assay.
Brundage-RA; Azadi-S; Meade-BJ; Siegel-PD; Weissman-DN
Toxicologist 2005 Mar; 84(Suppl 1):248
Western Red Cedar (WRC, Thuja plicata) induces sensitization and asthma after occupational exposure. Plicatic acid, a low molecular weight (LMW) compound present at high concentrations in WRC wood has been implicated as the active agent. Another wood product, abietic acid (ABA), a terpenoid present in the resin of conifer species, has also been identified as a LMW agent causing occupational sensitization and asthma. We used the mouse local lymph node assay to address the question of whether these agents could induce sensitization via the dermal route. WRC was extracted in water and the extract was lyophilized (WRC Extract). Mass spectrometry was consistent with plicatic acid being a major, but not the only, component of WRC extract. WRC extract and ABA were applied in concentrations of 12.5, 25, and 50% (w/v) to the ears of Balb/C mice. Vehicle treatment was used as a negative control and 30% -hexylcinnamaldehyde was used as a positive control. Neither WRC nor ABA caused increases in ear thickness, suggesting that neither was a dermal irritant. In vivo cell proliferation in draining lymph nodes was measured as 3H-thymidine incorporation following 3 days of exposure. Lymph node cell populations were evaluated for the presence of B220+ IgE+ B cells by flow cytometry on day 10, following 4 days of exposure. 3H-thymidine incorporation in draining lymph nodes was significantly increased by exposure to all three concentrations of WRC extract and the highest concentration of ABA (50%). Stimulation indices were: 3.4, 6.9, and 11.0 for 12.5%, 25%, and 50% WRC extract; and 3.0 for 50% ABA. Only the 50% WRC extract caused significant increases in B220+ IgE+ B cell percentage in draining nodes. Serum total IgE was increased 2 weeks after dermal exposure every other day to 25% and 50% WRC extract. Our results show that both WRC extract and ABA can induce sensitization by the dermal route and that WRC extract and ABA are weak dermal sensitizers (EC3 10% and 50%, respectively).
Sensitization; Acids; Lymph-nodes; Bronchial-asthma; Occupational-exposure; Wood; Wood-dusts; Laboratory-animals; Animals; Animal-studies; Mass-spectrometry; In-vivo-studies; Exposure-levels; Respiratory-system-disorders; Pulmonary-system-disorders
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana