Report Date: March 1997
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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
Introduction: Pentaerythritol triacrylate mixture was selected for evaluation in mice as a sensitizing agent for contact hypersensitivity Due to its widespread production and use there is a great potential for human exposure. Exposure to this compound occurs primarily by inhalation or dermal exposure. PEA is a component of radiation-cured and photocurable coatings of urethanes and epoxy resins. It is also used in the production of paints, sealants and coatings, acrylic glues and adhesives. PEA has extensive use in the printing industry It is an acrylic component of photopolymer and flexographic printing plates, flexographic inks and ultraviolet cured letterpress. It is also used in the production of ultraviolet curable decorative coatings and fast-drying ink systems for lithographic and web offset printing inks. Dermal studies in rabbits and guinea pigs have shown PEA to be an irritant and to cause dermal sensitization. There are numerous case studies of human irritation and sensitization arising from occupational exposure and studies using human volunteers have shown PEA to be a sensitizer. One of the major concerns with sensitization to PEA is its ability to cross-react with other multi-functional acrylates.
Design: The Pentaerythritol triacrylate mixture (approximately 10% pentaerythritol triacrylate) was obtained from NIEHS and supplied by Battelle. Dilutions were made in acetone which served as the vehicle Three assays were used in this assessment, a primary Irritancy Study, to screen for toxicity and determine the minimal irritating concentration and the maximal non-irritating concentration, and two assays, the Mouse Ear Swelling Test and the local lymph node assay, to test the dermal sensitizing potential of PEA.
For irritancy testing four mice per group were used to test six concentrations of test article in vehicle, vehicle alone and untreated controls. The lowest concentration of test article inducing a statistically significant increase in percent ear swelling when compared to the vehicle control was considered the MNC. The highest concentration not inducing a significant increase in percent ear swelling over the vehicle control was considered the MNC. Doses chosen for the hypersensitivity assays were based on the MIC and MNC. Pre-, 24 and 48 hr post-treatment ear measurements were taken and used to calculate the percent ear swelling Ear measurements from animals dosed with varying concentrations of test article were compared to the PEA background control group for significance After 3 consecutive days of dosing, animals were rested for 1 day and then injected with 'H-thymidine, 5 hours later the draining lymph nodes were dissected out and radioassayed.
Chemical exposed groups were compared to the vehicle control group for statistical significance. When a no effect level was not determined in this study a second study with lower concentrations was conducted.
Results: No signs of toxicity were seen in PEA exposed animals. The Minimal Irritating Concentration was determined to be 0.25% and the Maximal Non-Irritating Concentration to be 0.1%. A contact hypersensitivity response was not demonstrated by the MEST in PEA exposed animals. The positive control group in the MEST produced a statistically significant response at a sensitizing concentration of 0.25% and challenge concentration of 0.25% DNFB as compared to the 0.25% DNFB challenge only group. In the LLNA concentrations as low as 0.050% PEA and the positive control (0 25% DNFB) produced a significant response as compared to the vehicle treated group.
Conclusions: The Pentaerythritol triacrylate mixture (approximately 10% pentaerythritol triacrylate) was found to produce irritation at concentrations as low as 0.25%, Testing for sensitizing potential using the Mouse Ear Swelling test failed to indicate PEA as a contact sensitizer.. A positive response was seen in the Local Lymph Node Assay at concentrations as low as 0.0500"0. These data indicate the potential of PEA as a contact sensitizer.