The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP in March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Introduction: Acrylate esters have a widespread use in the manufacturing of numerous industrial and consumer products. They are most commonly used to produce polymers and resins used in such products as latex paint, fabric finishes, floor polishes, specialty plastics and dirt release agents. Occupational exposure to these compounds occurs primarily by inhalation or skin exposure. Butyl Acrylate (BAC) was selected for evaluation as a sensitizing agent for contact hypersensitivity in mice.
Design: Butyl Acrylate (BAC) was obtained from Aldrich Chemical Company as a clear liquid (99%, Lot #02320CY). 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 (MIC) and the Maximal Non-Irritating Concentration (MNC) and two assays, the Mouse Ear Swelling Test (MEST) and the Local Lymph Node Assay (LLNA), to test the dermal sensitizing potential of BAC.
For irritancy studies, nine mice were used to test four concentrations of test article in vehicle plus vehicle and untreated controls. Each mouse received a different treatment on each of its ears, one on the right ear and one on the left ear. The treatment combinations may be two different concentrations of test material, one concentration of test material and the vehicle, one concentration of the test material and no treatment, or the vehicle and no treatment. Each concentration of test material and the vehicle were tested three times. Animals were dosed on 4 consecutive days and checked daily for signs of morbidity. The lowest concentration of test article demonstrating significant irritation, as determined by the percent ear swelling at 24 hrs post last treatment, was considered the Minimal Irritating Concentration (MIC). The highest concentration not to demonstrate a significant irritation over the vehicle controls was considered the Maximal Non-Irritating Concentration (MNC). Because no irritating concentration was detected, 10, 20 and 30% BAC were chosen as the sensitizing doses to be used in the hypersensitivity assays.
The design for the MEST is shown in the table below. Animals were dosed on the back for 3 consecutive days, rested for 4 days and then challenged on the right ear. Pre, 24 and 48 hr post treatment ear measurements were taken and used to calculate the percent ear swelling. Measurements from animals dosed with varying concentrations of test article were compared to the BAC background control for significance.
|Group||Exp. Group||No. of Mice||Sensitization||Challenge|
|7||PC||8||0.25% DNFB||0.5% DNFB|
|Abbreviations: VH=vehicle; BC=background control; PB=positive background; PC=positive control; DNFB=2,4-Dinitrofluorobenzene|
The chemical concentrations and experimental groups used for the LLNA are shown in the table below. After 3 consecutive days of dosing, animals were rested for 1 day and then injected with 3H thymidine, lymph nodes were dissected out 5 hours later and radioassayed. Chemical exposed groups were compared to vehicle controls for statistical significance.
|Exp. Group||No. of Mice||Induction|
|Abbreviations: VH=vehicle; PC=positive control; DNFB=2,4-Dinitrofluorobenzene|
Results: There were no treatment related effects on survival or body weights. Irritancy studies tested concentrations up to 30% without detecting an irritating concentration. Because no irritating concentration was detected, 10, 20 and 30% BAC were chosen as the sensitizing doses to be used in the hypersensitivity assays. No statistically significant allergic contact hypersensitivity response was demonstrated by the MEST in mice sensitized with 10, 20 or 30% BAC either 24 or 48 hours following challenge. The positive control group produced a statistically significant contact hypersensitivity response at a sensitizing concentration of 0.25% and challenge concentration of 0.5% DNFB as compared to the 0.5% DNFB challenge only group. The DNFB challenge only group, dosed with 0.5% DNFB, showed a significant response when compared to the vehicle group. Concentrations of 20 and 30% BAC and 0.25% DNFB, the positive control, caused a significant response as compared to the vehicle treated group in the LLNA.
Conclusion: A significant allergic contact hypersensitivity response could be demonstrated in female B6C3F1 mice to butyl acrylate using the LLNA.
Report Date: September 1994