National Toxicology Program

National Toxicology Program
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NTP Report on the Assessment of Contact Hypersensitivity to Trimethylolpropane Triacrylate Mixture in Female BALB/c Mice (CASRN: 15625-89-5)

ABSTRACT

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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.

NTP Report Number IMM97003

Summary

Introduction: Trimethylolpropane triacrylate mixture (TMT) was selected for evaluation in mice for the potential to induce contact sensitization. Due to its widespread production and use there is great potential for human exposure. Exposure to this compound occurs primarily by inhalation or skin exposure. TMT is used in the printinig industry both as a component of photopolymer and flexographic printing plates and in the formulation of ultraviolet curable inks and electron beam irradiation curable coatings. TMT is used as a cross-linking agent and reactive diluent. It is found as an ingredient in acrylic glues, adhesives and anaerobic sealants. It is also found in polymers and resins used for specialty plastics, surface coatings and latex coatings. Further uses are found in the production of paper and wood impregnates, wire and cable extrusion and polymer impregnated concrete. Animal studies have shown TMT to be a dermal irritant in the in the mouse and rabbit. Studies using guinea pig models have shown TMT to have dermal sensitizing potential. There are numerous case studies of human skin irritation and senstization occuring following occupational exposure to TMIT. Animal studies have shown the potential for cross reactivity between TMT and other acrylates and methacrylate esters. Human studies have also shown the potential for cross reactivity between multifunctional acrylate monomers including TMT.

Design: The Trimethylolpropane triacrylate mixture 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 (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 TMT.

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 demonstrating a statistically significant increase in percent ear swelling when compared to vehicle control was considered the MIC. The highest concentration not demonstrating 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. The design for the MEST is shown in the table below (Table 1). 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 TMT background control group for significance. The chemical concentrations and experimental groups used for the LLNA are shown in the table below (Table 2). 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.

Table 1

Group Exp. Group No. of Mice Sensitization Challenge
1 VH 8 Vehicle Vehicle
2 BC 8 Vehicle MIC
3 D1 8 0.1 MNC MIC
4 D2 8 0.5 MNC MIC
5 D3 8 MNC MIC
6 BP 8 Vehicle 0.20% DNFB
7 PC 8 0.20% DNFB 0.20% DNFB
Abbreviations: VH=vehicle; BC=background control; MNC=maximal non-irritating concentration; MIC=mInimal irritating concentration: BP=background positive; PC=positive control; DNFB=2,4-Dinitrofluorobenzene

Table 2

Exp. Group No. of Mice Induction
VH 6 Vehicle
D1 6 0.5 MNC
D2 6 MNC
D3 6 MIC
PC 6 0.20% DNFB
Abbreviations: VH=vehicle; MIC=minimal irritating concentration; MNC=maximal non-irritating concentration; PC=positive control; DNFB=2,4-Dinitrofluorobenzene

Results: No signs of toxicity were seen in TMT 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 TMT exposed animals. The positive control group in the MEST produced a statistically significant response at a sensitizing concentration of 0.20% and challenge concentration of 0.20% DNFB as compared to the 0.20% DNFB challenge only group. In the LLNA trend analysis was significant at p < 0.05 but a statistically significant increase in lymph node cell proliferation was not reached at the highest concentration of TMT tested (0.25%).

Conclusions: The Trimethylolpropane triacrylate mixture was found to produce irritation at concentrations as low as 0.25%. Testing for sensitizing potential using the Mouse Ear Swelling Test and the Local Lymph Node Assay failed to indicate TMT as a contact sensitizer at the concentrations tested.

Report Date: January 1995

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