The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Pyrogallol or pyrogallic acid (1, 2, 3 trihydroxybenzene) is a reducing agent that produces a dark discoloration on oxidation. Both PYR and its oxidative product, purpurogallin, are known to be mutagenic. PYR was used as topical therapy for chronic plaque psoriasis in the early years of this century, and it is still used in some countries for resistant psoriasis. In addition, PYR has found extensive use as an antioxidant in industrial and commercial processes, including as a photographic developer, in the manufacture of dyes, as a component of hair and fur dye, as a tanning agent for leather, and in the production of a novel class of carbamate insecticides.
The objective of this study was to determine the potential for PYR to elicit an allergic response when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the local lymph node assay. In the solubility studies, PYR was found to be soluble at a concentration of 75% (w/v) in the acetone:olive oilp vehicle. Accordingly, the highest exposure level selected for LLNA, based on ICCVAM recommended protocol, was 50%. Four additional exposure levels of PYR were also tested. Thus, in the first LLNA, mice were sensitized to 2.5%, 5%, 10%, 25%, and 50% PYR. Since PYR at all the concentrations produced a significant increase in the proliferation of lymph node cells, two additional LLNAs were performed. The concentrations of PYR used in the second study were 0.5%, 1.0% and 2.5%, and, for the third study, concentrations of 0.25%, 0.5%, 1.0%, 2.5%, 5%, and 10% were used. Based on the results of the LLNA, a Primary Irritancy Assay study was conducted using exposure levels at 0.125%, 0.25%, 1.0%, 5%, and 10%. The data from the Irritancy Study showed that PYR is an irritant at a concentration as low as 0.125%. As demonstrated in the LLNA, a positive response was observed at the PYR concentration of 0.5% or higher. Thus, it seemed that the significantly increased proliferation observed in the LLNA might be due to the irritant effect of PYR. To further determine if PYR is primarily an irritant, two Mouse Ear Swelling Tests were performed. In the first mouse ear swelling test, mice were sensitized with PYR at concentrations of 0.25%, 1%, and 5%, and challenged with 0.25% of PYR. There was no significant difference when the naive, vehicle, and three dose groups were compared to background control at either 24 or 48 hour time point. In the second MEST, mice were sensitized with PYR at concentrations of 1% and 5%, and challenged with 1% of PYR. A significant increase in mouse ear thickness was observed at 66 hr after challenge in mice that were sensitized with 5% PYR. 1-fluoro-2,4-dinitrobenzene (2,4-dinitrofluorobenzene) was used as the positive control at a concentration of 0.15% for the irritancy test, LLNA, and MEST.
Taken together, these results demonstrate that PYR is a weak sensitizer but a strong irritant in female BALB/c mice. The positive response observed in the LLNAs is mainly due to the irritant effect of PYR.