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Skin Sensitizing Potency of Halogenated Platinum Salts.
Citation:
LEHMANN, D. M., W. C. WILLIAMS, C. B. COPELAND, E. BOYKIN, AND M. Selgrade. Skin Sensitizing Potency of Halogenated Platinum Salts. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2011.
Impact/Purpose:
In this study, we evaluated ammonium hexachloroplatinate (AHCP), ammonium tetrachloroplatinate (ATCP) and cis-dichlorodiamine (CDDP) using the local lymph node assay.
Description:
The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published that investigate whether there are differences in potencies of halogenated Pt salts. In this study, we evaluated ammonium hexachloroplatinate (AHCP), ammonium tetrachloroplatinate (ATCP) and cis-dichlorodiamine (CDDP) using the local lymph node assay. For 3 consecutive days, BALB/c mice were dosed topically on the dorsum of both ears with vehicle, 25% trimellitic anhydride (TMA, positive control) or one of 3 concentrations of Pt salt. On day 5, lymph nodes were harvested and single-cell suspensions were labeled ex vivo with [3H]methyl thymidine. Lymphocyte proliferation was determined by scintillation counting. Concentration-dependent increases in ear thickness and lymphocyte proliferation were observed for all 3 Pt salts. None of the doses tested resulted in a skin irritant response since erythema was minimal and the maximum increase in ear thickness was less than 25% (n =12). The EC3 values for AHCP, ATCP and CDDP were determined to be 0.58, 0.23 and 0.33%, respectively (n =12). In complementary studies, lymph node cells were labeled ex vivo with bromodeoxyuridine (BrdU) to investigate an alternative to radioisotopic labeling. Incorporation of BrdU was determined by ELISA. In this case, the EC2 values for AHCP, ATCP and CDDP were determined to be 0.12, 0.95 and 0.17%, respectively (n =6). The stimulation index of TMA was 4.6% (+/-1.2) and 2.9% (+/-0.3) in the radioisotope- and BrdU-labeling procedures, respectively. We conclude that AHCP, ATCP and CDDP are categorized as strong sensitizers according to the Globally Harmonized System for Classification and Labeling of Chemicals. Furthermore, these data suggest that BrdU labeling may not be as sensitive a procedure as labeling with radioisotope. This abstract does not reflect EPA policy.